WP1: The first objective “to increase understanding of the epidemiology of CWD strains detected in Europe and evaluate surveillance strategies, using sampling and population data from affected countries in Scandinavia” is deemed fulfilled to 80%. Finalising analyses and manuscripts in preparation remains. The second objective “To develop/adapt disease transmission models to predict the potential spread of CWD in Scandinavian reindeer populations” is deemed fulfilled to 20%, and will be completed later in the project.
Statistical models have been developed as a simulation tool to evaluate existing surveillance and assess the likelihood of CWD being absent from reindeer populations. In reindeer populations where CWD has not yet been detected, the probability of freedom-from-CWD has been estimated under a range of prevalence scenarios, and high probability of CWD absence was predicted in semi-domesticated reindeer neighbouring the region with infected wild reindeer. Surveillance data from other semi-domesticated reindeer populations show that there is a large variation in the probability of freedom-from-CWD in different districts of the Nordic countries, reflecting variation in numbers of samples analysed. In moose, older females are over-represented in CWD cases, and apparent clusters of cases may be explained by factors other than spread of infection.
WP2: The degree of completion of the objective “To identify Prion protein gene (PRNP) polymorphisms potentially associated with resistance to CWD in European cervids” is estimated at 45%. Sample collection from wild deer populations is complete in Norway and almost complete in France and Germany, and PRNP sequencing will be completed within the next 6 months. Work has started to produce purified recombinant prion protein (PrP) and cell lines expressing major cervid PrP variants for in vitro conversion assays planned in the second half of the project.
Tissue samples for PRNP sequence analysis have been collected from major wild deer populations across Norway, France and Germany. As well as previously described polymorphisms, two novel PRNP polymorphisms have been identified in French and German red deer, respectively. Selected cervid PRNP sequences have been cloned and expressed in bacterial expression systems to generate purified recombinant PrP for use in RT-QuIC in vitro conversion assays, and are also expressed in cell lines to provide substrate for PMCA assays.
WP3. The estimated degree of completion of the objective “To assess the likelihood that prions from European CWD isolates can transmit to livestock species and humans, using in vitro and in vivo models” is 35-40%. While most mouse transmission experiments have been initiated, the moratorium on prion research in France has delayed the start of some experiments in human PrP transgenic mice, and the sharing of a panel of isolates for in vitro experiments. It is anticipated that most of the in vitro work can be completed within the original project timeline, but completion of the mouse experiments would require an extension of the project.
A panel of European CWD isolates, with North American CWD isolates as reference, was shared among partners for inoculation into transgenic mouse lines expressing bovine, ovine, porcine or human PrP. Selected CWD isolates that previously transmitted infection to transgenic mice expressing ovine or bovine PrP have been inoculated into human-PrP transgenic mice to evaluate whether zoonotic potential is modified after passage in an intermediate species. Transmission experiments are still in progress, but data so far suggests that the zoonotic potential of CWD isolates assayed is not high.
Chronic wasting disease (CWD) is an emergent prion disease first identified the late 1960s, which has since spread rapidly among cervids in North America with devastating consequences for populations in some areas. Among prion diseases, BSE can transmit to humans and has resulted in >220 deaths from variant CJD. Although there is no epidemiological evidence to date suggesting spread of CWD to humans, recent reports of experimental oral transmission to non-human primates give cause for concern. In Europe the first cases of CWD were identified in 2016 in wild reindeer (20) in Norway. Additional cases were found in moose in Norway (7), Finland (2) and Sweden (4), and 1 red deer in Norway. Biochemical properties of prions from Norwegian CWD cases and their transmission in rodent models have shown that the European and North America CWD strains are different. This means that risk assessments and control strategies cannot not be solely based on evidence from CWD in North America, and that further research specific to the European context is urgently required. This project will integrate research on the epidemiology and population dynamics of the disease in affected countries, and through mathematical and statistical models, will evaluate surveillance strategies. The outcomes will have an impact on the modelling of CWD spread, and may also identify PRNP alleles associated with disease resistance that could be used in selective breeding programmes for disease control. The risks of transmission of European CWD isolates to sheep, cattle, pigs and humans will be assessed using the in vitro method PMCA and in vivo models (transgenic mice expressing PrP from the target species). Understanding which CWD strains are most likely to cross species barriers, and which species are most at risk, will allow better targeting of surveillance and control measures.