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Prions are infectious proteins causing fatal, transmissible neurodegenerative diseases of animals and humans. Replication involves template-directed refolding of host encoded prion protein, PrPC, by its infectious conformation, PrPSc. Following its discovery in captive Colorado deer in 1967, uncontrollable contagious transmission of chronic wasting disease (CWD) led to an expanded geographic range in increasing numbers of free-ranging and captive North American (NA) cervids. Some five decades later, detection of PrPSc in free-ranging Norwegian (NO) reindeer and moose marked the first indication of CWD in Europe. To assess the properties of these emergent NO prions and compare them with NA CWD we used transgenic (Tg) and gene targeted (Gt) mice expressing PrP with glutamine (Q) or glutamate (E) at residue 226, a variation in wild type cervid PrP which influences prion strain selection in NA deer and elk. Transmissions of NO moose and reindeer prions to Tg and Gt mice recapitulated the characteristic features of CWD in natural hosts, revealing novel prion strains with disease kinetics, neuropathological profiles, and capacities to infect lymphoid tissues and cultured cells that were distinct from those causing NA CWD. In support of strain variation, PrPSc conformers comprising emergent NO moose and reindeer CWD were subject to selective effects imposed by variation at residue 226 that were different from those controlling established NA CWD. Transmission of particular NO moose CWD prions in mice expressing E at 226 resulted in selection of a kinetically optimized conformer, subsequent transmission of which revealed properties consistent with NA CWD. These findings illustrate the potential for adaptive selection of strain conformers with improved fitness during propagation of unstable NO prions. Their potential for contagious transmission has implications for risk analyses and management of emergent European CWD. Finally, we found that Gt mice expressing physiologically controlled PrP levels recapitulated the lymphotropic properties of naturally occurring CWD strains resulting in improved susceptibilities to emergent NO reindeer prions compared with over-expressing Tg counterparts. These findings underscore the refined advantages of Gt models for exploring the mechanisms and impacts of strain selection in peripheral compartments during natural prion transmission. Author summary: Prions cause fatal, transmissible neurodegenerative diseases in animals and humans. They are composed of an infectious, neurotoxic protein (PrP) which replicates by imposing pathogenic conformations on its normal, host-encoded counterpart. Chronic wasting disease (CWD) is a contagious prion disorder threatening increasing numbers of free-ranging and captive North American deer, elk, and moose. While CWD detection in Norwegian reindeer and moose in 2016 marked the advent of disease in Europe, its origins and relationship to North American CWD were initially unclear. Here we show, using mice engineered to express deer or elk PrP, that Norwegian reindeer and moose CWD are caused by novel prion strains with properties distinct from those of North American CWD. We found that selection and propagation of North American and Norwegian CWD strains was controlled by a key amino acid residue in host PrP. We also found that particular Norwegian isolates adapted during their propagation in mice to produce prions with characteristics of the North American strain. Our findings defining the transmission profiles of novel Norwegian prions and their unstable potential to produce adapted strains with improved fitness for contagious transmission have implications for risk analyses and management of emergent European CWD. [ABSTRACT FROM AUTHOR]

International policy for the management of wildlife disease(s) plays an important role for concerted action, and changes to policy should be evidence‐based and updated as new evidence accumulates. Management of chronic wasting disease (CWD), the prion disease affecting cervids, is based on its highly contagious nature relative to most other prion diseases. These management actions are particularly invasive, with considerable biological and economic consequences.A novel type of CWD has been discovered in moose Alces alces and red deer Cervus elaphus, with prions restricted to the central nervous system (CNS). Prions in tissue outside the CNS are an indication of the contagiousness of a prion disease. As such, for this novel type of CWD, there is a lower likelihood of horizontal transmission under natural conditions. Furthermore, infected individuals were older (mean 15 years), and cases appeared with limited clustering in space and time; hence, with no indication of an epidemic outbreak.Policy implications. The annual harvest of approximately 4 million cervids in Europe each year generates considerable cultural and economic value. 'Stamping out' policies would be inefficient and inappropriate to control diseases with no horizontal transmission among live animals, and banning the export of meat from a region after detection of a positively tested animal would make little sense in the case of sporadic disease. The novel type of chronic wasting disease (CWD) with epidemiological characteristics clearly different from 'classical' and contagious CWD calls for differentiated management strategies to avoid unnecessarily invasive actions. [ABSTRACT FROM AUTHOR]

Classical bovine spongiform encephalopathy (BSE) is the only zoonotic prion disease described to date. Although the zoonotic potential of atypical BSE prions have been partially studied, an extensive analysis is still needed. We conducted a systematic study by inoculating atypical BSE isolates from different countries in Europe into transgenic mice overexpressing human prion protein (PrP): TgMet129, TgMet/Val129, and TgVal129. L-type BSE showed a higher zoonotic potential in TgMet129 mice than classical BSE, whereas Val129-PrP variant was a strong molecular protector against L-type BSE prions, even in heterozygosis. H-type BSE could not be transmitted to any of the mice. We also adapted 1 H- and 1 L-type BSE isolate to sheep-PrP transgenic mice and inoculated them into human-PrP transgenic mice. Atypical BSE prions showed a modification in their zoonotic ability after adaptation to sheep-PrP producing agents able to infect TgMet129 and TgVal129, bearing features that make them indistinguishable of sporadic Creutzfeldt-Jakob disease prions. [ABSTRACT FROM AUTHOR]

Abstract: The transmission of bovine spongiform encephalopathy (BSE) to human beings and the spread of chronic wasting disease (CWD) among cervids have prompted concerns about zoonotic transmission of prion diseases. Travel to the United Kingdom and other European countries, hunting for deer or elk, and venison consumption could result in the exposure of US residents to the agents that cause BSE and CWD. The Foodborne Diseases Active Surveillance Network 2006-2007 population survey was used to assess the prevalence of these behaviors among residents of 10 catchment areas across the United States. Of 17,372 survey respondents, 19.4% reported travel to the United Kingdom since 1980, and 29.5% reported travel to any of the nine European countries considered to be BSE-endemic since 1980. The proportion of respondents who had ever hunted deer or elk was 18.5%, and 1.2% had hunted deer or elk in a CWD–endemic area. More than two thirds (67.4%) reported having ever eaten deer or elk meat. Respondents who traveled spent more time in the United Kingdom (median 14 days) than in any other BSE-endemic country. Of the 11,635 respondents who had consumed venison, 59.8% ate venison at most one to two times during their year of highest consumption, and 88.6% had obtained all of their meat from the wild. The survey results were useful in determining the prevalence and frequency of behaviors that could be important factors for foodborne prion transmission. [Copyright &y& Elsevier]

The incidence of BSE in Europe is in continued decline. At present, iatrogenic transmission from person to person is considered a serious threat to public health. This report of the International Society of Blood Transfusion Working Party on Transmissible Spongiform Encephalopathy will focus on the state of the art in relation to blood components and plasma safety. Latest information on the pathogenicity of the infectious agent, the frequency and dynamics of infection in blood and transfusion transmissibility will be documented. Preventive measures including donor deferral policies, technologies for prion removal from labile blood components and for prion detection in plasma, the absence of a sensitive and rapid reference assay able to confirm the positive results from any putative blood screening assay will be updated. At last, as many uncertainties remain and a number of assumptions await confirmation, the areas to continue to explore are listed. [ABSTRACT FROM AUTHOR]

Since 2004, a novel bovine spongiform encephalopathy (BSE), distinct from the conventional 'classical BSE' (C-BSE), has been reported as an atypical BSE. Atypical BSE is detected mostly in aged cattle, and it is suggested that atypical BSE may occur spontaneously. Relaxation of the relevant countermeasures such as feed ban, which prevents the use of bovine meat-and-bone meal as feed, has been discussed in recent years owing to the decrease in C-BSE cases. If atypical BSE occurs spontaneously without exposure to an agent called abnormal prion protein (PrP Sc ), complete removal of these measures will be difficult. In this study, we verified the possibility that L-BSE, which is a subtype of atypical BSE, occurs spontaneously. We first hypothesized that L-BSE occurs only through the process of infection via oral exposure. If the hypothesis was true, the infection of L-BSE would be mostly limited to calves under 1 year of age due to their high susceptibility, and the feed ban would effectively reduce the number of infected calves by birth cohort. Thus, we created a mathematical model to estimate the number of infected calves by birth cohort and compared the effectiveness of the feed ban on C-BSE and L-BSE. The number of tested animals and detected cases in nine European countries were used for this analysis. Our results showed that the estimated number of infected calves in the birth cohort indicated that feed ban was less effective on L-BSE. This result supports the alternative hypothesis that at least a part of the L-BSE can occur without infection via oral exposure. Our results suggest that the complete abolition of countermeasures, such as feed ban, should be discussed carefully. As for the occurrence mechanism, although there remains uncertainty to reach conclusions, it is reasonable to assume that L-BSE can occur spontaneously at present., (© 2021 Wiley-VCH GmbH.)

The diversity of goat scrapie strains in Europe has recently been studied using bioassays in a wide collection of rodent models, resulting in the classification of classical scrapie into four different categories. However, the sole use of the first passage does not lead to isolate adaptation and identification of the strains involved and might therefore lead to misclassification of some scrapie isolates. Therefore, this work reports the complete transmission study of a wide collection of goat transmissible spongiform encephalopathy (TSE) isolates by intracranial inoculation in two transgenic mouse lines overexpressing either small ruminant (TgGoat-ARQ) or bovine (TgBov) PrPC. To compare scrapie strains in sheep and goats, sheep scrapie isolates from different European countries were also included in the study. Once the species barrier phenomenon was overcome, an accurate classification of the isolates was attained. Thus, the use of just two rodent models allowed us to fully differentiate at least four different classical scrapie strains in small ruminants and to identify isolates containing mixtures of strains. This work reinforces the idea that classical scrapie in small ruminants is a prion disease caused by multiple different prion strains and not by a single strain, as is the case for epidemic classical bovine spongiform encephalopathy (BSE-C). In addition, the clear dissimilarity between the different scrapie strains and BSE-C does not support the idea that classical scrapie is the origin of epidemic BSE-C. [ABSTRACT FROM AUTHOR]

The article offers regulatory updates related to medical products and patents in Europe. It discusses amending directives for 2001/83/EC on community code to medicinal products for human use in relation to the prevention of the entry for falsified medicinal products. It also mentions the judgment on the eradication of transmissible spongiform encephalopathies (TSEs) known as prion diseases which are a group of progressive conditions affecting the brain and nervous system.

Cervids are keystone species in ecosystems and are associated with enormous cultural and economic value. Chronic wasting disease (CWD) is a fatal prion disease spreading in North American cervid populations. The 2016 emergence of CWD in Europe makes it urgent to understand the basics of CWD and to assess the extent to which current CWD knowledge is transferable to Europe. CWD is difficult to detect in the early stages due to very low prevalence and slow growth rates. The negative population effect of CWD is mainly due to increased female adult mortality, as infected individuals continue to reproduce. It may take decades before CWD leads to population declines. The population dynamics of mule deer are affected more by CWD than those of white-tailed deer, which in turn are more affected than those of elk, and depending on other factors limiting the populations. Species- and population-specific differences in dynamical consequences are linked to the balance among the rates of transmission, incubation period (linked to the prion protein gene, PRNP), and reproductive rates. This make it difficult to predict effects of CWD in Europe with other cervids, but the dynamic impact may be marked to cervid populations over the long term. The process of spillover across the species barrier is not well understood. Occasional spillover to moose without an apparent epizootic suggests specific conditions can limit CWD. Frequency-dependent transmission or weak density-dependent transmission makes it difficult to control CWD using density reductions through harvest and/or culling. CWD is difficult to eradicate once it becomes endemic, and it calls for immediate management actions. These actions involve extensive culling, fencing, and ceasing of wildlife feeding and are likely to cause significant controversy. [ABSTRACT FROM AUTHOR]

For European researchers over age 60, staying put is not an option. Many European countries impose a mandatory retirement age for public employees, ranging from a low of 60 in France to a high of 67 in Norway and Sweden. Those who are determined to stay at the bench past retirement often live a precarious life, relying on the generosity of younger colleagues for lab space and access to infrastructure. Some of the biggest names in European science have managed to cut special deals to stay on, but failing that, the only alternative is to seek employment where there are no such age restrictions, most often in the U.S. In order to continue his work on prion diseases after his retirement from the University of Zürich, 72-year-old molecular biologist and biotechnology pioneer Charles Weissmann left Switzerland in 1999 for the Medical Research Council Prion Unit at University College London.

Discusses panic in Europe over the transmission of bovine spongiform encephalopathy (BSE), also known as mad cow disease. Launch of testing on carcasses of cattle that have been slaughtered for human consumption; Release of a report which exposed the failings of the agricultural and meat-producing sectors in the United Kingdon to deal with the disease; Background of prion disease.