Zoonotic risk assessment for chronic wasting disease rests on three experimental systems that answer different questions, and they do not agree. For the disease in cervids see chronic wasting disease; for the hunter-facing version of this page see deer, venison and CWD.
What did the humanised mouse challenge show?
Wadsworth and colleagues inoculated brain tissue from CWD-infected Norwegian reindeer and moose into transgenic mice overexpressing human prion protein. After prolonged post-inoculation survival periods no evidence of prion transmission was seen, and the authors state that this suggests the zoonotic potential of these isolates is low.
A transmission experiment that ends without disease bounds risk only within its own design. The relevant constraints are the route (intracerebral inoculation models a different exposure from eating meat), the single transgenic line and its expression level, the isolates used, and the absence of a second passage in the published report. Negative first-passage results in humanised mice have previously been followed by transmission on subpassage for other agents, which is why these experiments are normally read alongside in vitro conversion data.
What do conversion assays suggest?
Pritzkow and colleagues took CWD isolates from six cervid species and measured how efficiently each sustained prion conversion in protein misfolding cyclic amplification using normal prion protein from several mammals, including human. They define a spillover index for conversion of non-human substrates and a zoonotic potential index for conversion of human substrate. Their data suggest that reindeer and red deer isolates from Norway were the most transmissible to other mammals, while North American CWD isolates were more prone to generate human prions in vitro. They conclude that Norwegian and North American CWD correspond to different strains with distinct spillover and zoonotic potentials.
The two results are compatible. The humanised mouse experiment tested Norwegian isolates, which the conversion work places at the lower end for human substrate conversion. No equivalent humanised mouse challenge with the North American isolates that scored highest in vitro is reported in the sources read here. An in vitro conversion index is also not a measure of infectivity in an animal.
Are the European and North American agents the same?
Nonno and colleagues addressed this by classical strain typing, transmitting and adapting isolates in bank voles. Norwegian CWD prions produced incubation times, neuropathology, regional distribution of misfolded prion protein and protease-resistant core size that differed from North American CWD. They conclude that Norwegian strains are distinct, so the highly contagious North American agent is not the proximate cause of the Norwegian cases, and they report unexpected variability within Norway, with reindeer and moose carrying different strains. Their closing recommendation is that the zoonotic potential of the new European strains needs assessing in its own right.
Strain multiplicity is the central complication for risk assessment. A conclusion drawn from one isolate does not transfer to another, and surveillance in the two continents detects different kinds of case, which biases the isolate sets available for comparison.
What is the regulatory reading?
The EFSA BIOHAZ Panel’s third CWD update, published in November 2019, states that preliminary data support the contention that European and North American CWD strains differ and suggest strain diversity within European cervids, that current data allow no conclusion on what strain diversity implies for transmissibility, pathogenesis or prevalence, and that available data allow no conclusion on the zoonotic potential of North American or European isolates. On exposure, the opinion states that the risk to humans through meat consumption cannot be directly assessed, and that consumers of meat, meat products and offal from CWD-infected cervids will be exposed to the agent. Measures to reduce dietary exposure are described as applicable, with exclusion of whole carcasses of infected animals from the food chain among them.
That is the position an agency reaches when the experimental systems disagree: exposure is characterised, risk is not quantified.
What experiment is running now?
The Norwegian Veterinary Institute reported in December 2024 that thirteen reindeer calves from Filefjell Reinlag had been selected for infection trials taking place in Canada, the first such experiment using Norwegian reindeer and prions from Norwegian wild reindeer, within the international project Emerging CWD led by Sylvie Benestad. The institute states that the project investigates disease progression, the potential for CWD strains to spread among deer species, and the risk of infecting new species including humans. Earlier trials used North American reindeer and North American CWD prions.
Results from a cervid transmission study of this kind take years, and the institute’s page describes the work as ongoing rather than reporting outcomes. Related pages: biosafety, blood and plasma and decontamination.
Sources for this page
- Wadsworth JDF and others (2022) Humanized transgenic mice are resistant to chronic wasting disease prions from Norwegian reindeer and moose, J Infect Dis 226(5):933-937
- Pritzkow S and others (2022) North American and Norwegian chronic wasting disease prions exhibit different potential for interspecies transmission and zoonotic risk, J Infect Dis 225(3):542-551
- Nonno R and others (2020) Studies in bank voles reveal strain differences between chronic wasting disease prions from Norway and North America, PNAS 117(49):31417-31426
- EFSA BIOHAZ Panel (2019) Update on chronic wasting disease (CWD) III, EFSA Journal 17(11):e05863
- Norwegian Veterinary Institute: Can Norwegian reindeer provide new answers about Chronic Wasting Disease? (19 December 2024)