Animal Transmissible Spongiform Encephalopathies Research Articles

Prions and animal transmissible spongiform encephalopathies

Background. Transmissible spongiform encephalopathies (TSEs) or prion diseases are a unique group of neurodegenerative diseases of animals and humans, which always have a fatal outcome and are transmissible among animals of the same or different species. Scope and Approach. The aim of this work is to review some recent data about animal TSEs, with the emphasis on their causative agents and zoonotic potential, and to discuss why the surveillance and control measures over animal TSEs should remain in force. Key Findings and Conclusions. We still have incomplete knowledge of prions and prion diseases. Scrapie has been present for a very long time and controlled with varied success. Bovine spongiform encephalopathy (BSE) emerged unnoticed, and spread within a few years to epidemic proportions, entailing enormous economic consequences and public concerns. Currently, the classical BSE epidemic is under control, but atypical cases do, and probably will, persist in bovine populations. The Chronic Wasting Disease (CWD) of the cervids has been spreading in North America and has recently been detected in Europe. Preventive measures for the control of classical BSE remain in force, including the feed ban and removal of specified risk materials. However, active BSE surveillance has considerably decreased. In the absence of such preventive and control measures, atypical BSE cases in healthy slaughtered bovines might persist in the human food chain, and BSE prions might resurface. Moreover, other prion strains might emerge and spread undetected if the appropriate preventive and surveillance measures were to cease, leaving behind inestimable consequences.

Defining and Assessing Analytical Performance Criteria for Transmissible Spongiform Encephalopathy–Detecting Amyloid Seeding Assays

Transmissible spongiform encephalopathies (TSEs) are infectious, fatal neurodegenerative diseases that affect production animal health, and thus human food safety. Enhanced TSE detection methods mimic the conjectured basis for prion replication, invitro; biological matrices can be tested for prion activity via their ability to convert recombinant cellular prion protein (PrP) into amyloid fibrils; fluorescent spectra changes of amyloid-binding fluorophores in the reaction vessel detect fibril formation. Invitro PrP conversion techniques have high analytical sensitivity for prions, comparable with that of bioassays, yet no such protocol has gained regulatory approval for use in animal TSE surveillance programs. This study describes a timed invitro PrP conversion protocol with accurate, well-defined analytical criteria based on probability density and mass functions of TSE(+) and TSE(-) associated thioflavin T signal times, a new approach within this field. The prion detection model used is elk chronic wasting disease (CWD) in brain tissues. The protocol and analytical criteria proved as sensitive for elk CWD as two bioassay models, and upward of approximately 1.2 log10 more sensitive than the most sensitive TSE rapid test we assessed. Furthermore, we substantiate that timing invitro PrP conversion may be used to titrate TSEinfectivity, and, as a result, provide a comprehensive extrapolation of analytical sensitivity differences between bioassay, TSE rapid tests, and invitro PrP conversion for elk CWD.

Sterilization and Disposal of Agricultural Quarantine Waste

Approximately 150 million people and almost $40 billion worth of agricultural commodities go through U.S. international ports annually. Ports seize animal and plant products potentially contaminated with high risk diseases that then must be decontaminated before entering the waste stream. Currently, there are only 3 methods of decontamination accepted by the Animal Plant and Health Inspection Service at U.S. ports and borders including incineration, high temperature cooking, and discharge of ground waste as sewage. In this study we assess the efficacy of a relatively new decontamination technology, alkaline digestion, to mitigate infectious agents. Transmissible Spongiform Encephalopathies (TSEs), a member of the protein misfolding diseases (ex: Alzheimer’s and Parkinson’s Diseases), were chosen as the infectious agent for this study because they rank as the hardest to kill microbe/pathogen, affect both human and animal species worldwide and are shed by infected hosts into the environment establishing highly infectious biota. Chronic wasting disease (CWD), an emerging TSE of cervid species (deer, elk, moose) in North America, has recently been spotlighted as a potential concern for European countries, and recapitulates human and animal TSE pathogenesis and shedding. For these reasons CWD is ideal for mitigation studies. We processed CWD positive and negative materials by alkaline digestion under standard temperature and pressure at time intervals of 2, 4, and 6 h. Samples were retrieved after digestion, were neutralized and inoculated intracerebrally into transgenic mice expressing the cervid protein to determine remaining prion infectivity. In addition, the samples (pre and post alkaline digestion) were tested for amplification competent prions by Protein Misfolding Cyclic Amplification (PMCA). Preliminary results suggest a lack of amplification competent prions in samples processed by alkaline digestion at 2, 4, and 6 h cycles as compared to nondigested samples. This work will provide a basis for future studies designed to unravel the mechanisms associated with the ability of prions to bind surfaces enhancing prion mitigation strategies for TSEs and by extension, other protein misfolding diseases.

Scientific Opinion on a request for a review of a scientific publication concerning the zoonotic potential of ovine scrapie prions

The factors that modulate the transmissibility of Transmissible Spongiform Encephalopathies (TSE) and the approaches for the study of their zoonotic potential are reviewed. The paper ‘ Evidence for zoonotic potential of ovine scrapie prions’ by Cassard et al. (2014) is scientifically appraised, focussing on the experimental design, the results and the conclusions. The paper provides evidence in a laboratory experiment that some Classical scrapie isolates can propagate in humanised transgenic mice and produce prions that on second passage are similar to those causing one form of sporadic Creutzfeldt-Jakob disease (sCJD). It is concluded that the results from the study raise the possibility that scrapie prions have the potential to be zoonotic, but do not provide evidence that transmission can or does take place under field conditions. The conclusions of the 2011 ECDC-EFSA ‘ Joint Scientific Opinion on any possible epidemiological or molecular association between TSEs in animals and humans’ are reviewed in the light of the new scientific evidence available since its publication. This supports and strengthens the conclusions of that opinion with regard to the potential for some animal TSE to be zoonotic, but does not provide evidence of a causal link between Classical or Atypical scrapie and human TSE. Current evidence does not establish this link, and no consistent risk factors have been identified for sCJD. The possibility of scrapie-related public health risks from the consumption of ovine products cannot be assessed. Recommendations are formulated on further studies and data that are needed to investigate the zoonotic potential of animal TSE and to estimate the amount of infectivity from TSE-infected products sourced from small ruminants and entering the food chain in the European Union.

The evolution of the prevalence of classical scrapie in sheep in Great Britain using surveillance data between 2005 and 2012

After the decline of the Bovine Spongiform Encephalopathy (BSE) epidemic in Great Britain (GB), scrapie remains the most prevalent animal Transmissible Spongiform Encephalopathy (TSE) present in GB. A number of control measures have been implemented for classical scrapie, and since 2005 there has been a large reduction in the number of observed cases. The objective of this study is to estimate two measures of disease frequency using up to date surveillance data collected during and after the implementation of different control measures established since 2004, and breeding for resistance schemes that ran from 2001 until 2009. This would enable an assessment of the effectiveness of both the breeding for resistance programme and the compulsory eradication measures in reducing the prevalence of scrapie in GB. Evaluation of the sensitivity of the rapid post-mortem test for scrapie indicated that it detected scrapie in the last 25% of the incubation period. A back-calculation model was developed to estimate the prevalence of infection at animal and flock-level. The results of the model indicated a mean drop of infection prevalence of 31% each year, leading to a 90% drop in infection prevalence between 2005, with an estimate of 5737 infected sheep in GB in 2012.The risks of classical scrapie infection in animals with genotypes of National Scrapie Plan Types I–IV (all other genotypes), relative to Type V (all genotypes containing V136 R154 Q171 and not A136 R154 R171), were estimated to be: 0, 0.0008, 0.07, and 0.21 respectively. The model estimated a very low rate of reporting of clinical suspects and a large decline from 2007 of the probability of a sheep being reported as a clinical suspect. The model also estimated that the expected number of sheep holdings with classical scrapie in 2012 was 215 (95% confidence interval: 33–437), out of a total of approximately 72,000 sheep holdings in GB. Model estimates indicate that the prevalence in 2012 has dropped to 10% of that in 2005, showing the effectiveness of the control measures. It also shows a bias in the destination of infected animals, with the majority of infected animals being detected in the fallen stock surveillance stream, and an extremely low proportion of animals detected as clinical suspects; this is very important in terms of the design of surveillance schemes for classical scrapie.

Prion protein interaction with soil humic substances: environmental implications.

Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative disorders caused by prions. Animal TSE include scrapie in sheep and goats, and chronic wasting disease (CWD) in cervids. Effective management of scrapie in many parts of the world, and of CWD in North American deer population is complicated by the persistence of prions in the environment. After shedding from diseased animals, prions persist in soil, withstanding biotic and abiotic degradation. As soil is a complex, multi-component system of both mineral and organic components, it is important to understand which soil compounds may interact with prions and thus contribute to disease transmission. Several studies have investigated the role of different soil minerals in prion adsorption and infectivity; we focused our attention on the interaction of soil organic components, the humic substances (HS), with recombinant prion protein (recPrP) material. We evaluated the kinetics of recPrP adsorption, providing a structural and biochemical characterization of chemical adducts using different experimental approaches. Here we show that HS act as potent anti-prion agents in prion infected neuronal cells and in the amyloid seeding assays: HS adsorb both recPrP and prions, thus sequestering them from the prion replication process. We interpreted our findings as highly relevant from an environmental point of view, as the adsorption of prions in HS may affect their availability and consequently hinder the environmental transmission of prion diseases in ruminants.

In Vitro Detection of prionemia in TSE-Infected Cervids and Hamsters

Blood-borne transmission of infectious prions during the symptomatic and asymptomatic stages of disease occurs for both human and animal transmissible spongiform encephalopathies (TSEs). The geographical distribution of the cervid TSE, chronic wasting disease (CWD), continues to spread across North America and the prospective number of individuals harboring an asymptomatic infection of human variant Creutzfeldt-Jakob Disease (vCJD) in the United Kingdom has been projected to be ~1 in 3000 residents. Thus, it is important to monitor cervid and human blood products to ensure herd health and human safety. Current methods for detecting blood-associated prions rely primarily upon bioassay in laboratory animals. While bioassay provides high sensitivity and specificity, it requires many months, animals, and it is costly. Here we report modification of the real time quaking-induced conversion (RT-QuIC) assay to detect blood-borne prions in whole blood from prion-infected preclinical white-tailed deer, muntjac deer, and Syrian hamsters, attaining sensitivity of >90% while maintaining 100% specificity. Our results indicate that RT-QuIC methodology as modified can provide consistent and reliable detection of blood-borne prions in preclinical and symptomatic stages of two animal TSEs, offering promise for prionemia detection in other species, including humans.

Functional Genomics Approach for Identification of Molecular Processes Underlying Neurodegenerative Disorders in Prion Diseases

Prion diseases or transmissible spongiform encephalopathies (TSEs) are infectious neurodegenerative disorders leading to death. These include Cresutzfeldt-Jakob disease (CJD), familial, sporadic and variant CJD and kuru in humans; and animal TSEs include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) of mule deer and elk, and transmissible mink encephalopathy. All these TSEs share common pathological features such as accumulation of mis-folded prion proteins in the central nervous system leading to cellular dysfunction and cell death. It is important to characterize the molecular pathways and events leading to prion induced neurodegeneration. Here we discuss the impact of the functional genomics approaches including microarrays, subtractive hybridization and microRNA profiling in elucidating transcriptional cascades at different stages of disease. Many of these transcriptional changes have been observed in multiple neurodegenerative diseases which may aid in identification of biomarkers for disease. A comprehensive characterization of expression profiles implicated in neurodegenerative disorders will undoubtedly advance our understanding on neuropathology and dysfunction during prion disease and other neurodegenerative disorders. We also present an outlook on the future work which may focus on analysis of structural genetic variation, genome and transcriptome sequencing using next generation sequencing with an integrated approach on animal and human TSE related studies.

Reduction of protein kinase MARK4 in the brains of experimental scrapie rodents and human prion disease correlates with deposits of PrPSc

Microtubule affinity-regulating kinase 4 (MARK4) belongs to a family of kinases that are able to actively phosphorylate the neuronal microtubule-associate proteins (MAPs), such as tau, MAP2 and the ubiquitous MAP4. Abnormal changes in tubulin and the profiles of tau have been previously reported in the human brain and animal transmissible spongiform encephalopathies (TSEs), which may be associated with abnormal alterations of various cellular kinases. To elucidate the possible role of MARK4 in TSE pathogenesis, the MARK4 levels in the brain tissues of scrapie-infected rodents and human prion diseases were evaluated using western blotting and immunohistochemical assays. The results revealed that at terminal stages of the diseases, MARK4 levels in the brain tissues of the scrapie 263K-infected hamsters, 139A-infected mice and a case of Creutzfeldt-Jakob disease (CJD, G114V gCJD) correlated with amounts of PrP(Sc) deposits that were almost undetectable. On the other hand MARK4 signals were noticeable in the brain tissues of a fatal familial insomnia (FFI) patient without PrP(Sc). The reduction of MARK4 was closely related to the prolonged incubation times. These results could be reproduced in SK-N-SH and PC12 cell lines after being exposed to the synthetic peptide PrP106-126. Accordingly, the levels of phosphorylated tau at Ser262 (p-tau262) in cultured cells exposed to PrP106-126, or the ratios of p-tau262/total tau in the brain tissues of 263K-infected hamsters were also significantly decreased. According to our data there is a correlation between a TSE pathological-associated decline of MARK4 in the brain tissues with the deposits of PrP(Sc). Reduction of MARK4 will result in abnormalities of tau phosphorylation, and possibly induce further detachment of microtubules and hinder microtubule transportation.

Public Risk Perception of Relaxation of Transmissible Spongiform Encephalopathies (Tse) Measures in Europe

The so-called “TSE roadmap” was published by the European Commission on July 15, 2005. The transmissible spongiform encephalopathy (TSE) roadmap suggests relaxation of bovine spongiform encephalopathy (BSE) in cattle and other animal transmissible spongiform encephalopathies measures in the short, medium, and long term. According to the TSE roadmap, “Any relaxation of BSE measures following the scientific assessment should be initiated by an open discussion with all stakeholders and supported by a strong communication strategy” (European Commission 2005, 5). Bearing this in mind, a social scientific project was designed to (1) involve different stakeholder groups, governmental risk managers, and their scientific advisors and (2) obtain their perception of the TSE roadmap and of its implications for precautionary consumer protection in five European Union (EU) Member States. This study describes the risk perception and risk management of TSE in Europe as exemplified by the TSE roadmap. The following query guided the international comparative study: How is TSE risk perceived by four interviewed stakeholder groups in five studied countries? The risk perceptions of TSE of risk managers from the ministries in charge in Belgium, France, Germany, Italy, and the United Kingdom, as well as their scientific advisors and stakeholder groups, were determined. The stakeholder groups were from three different areas involved with TSE, including farmers, consumers, and the meat/food industry. The issue to be addressed is roadmapping an adequate instrument for stakeholder involvement and for risk decision making.

Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008

Background: Surveillance of Creutzfeldt-Jakob disease (CJD) is still an important issue because of the variant CJD epidemic, which is in decline and also because of the emergence of novel forms of animal transmissible spongiform encephalopathy with zoonotic potential and the risk of nosocomial and blood transfusion-related transmission. Active surveillance has been implemented in most European countries and requires important human resources and funding. Here, we studied whether national mortality and morbidity statistics can be used as reliable indicators. Methods: CJD data collected by the French national CJD surveillance centre were compared with data registered in the national mortality statistics. Results: From 2000 to 2008, the two sources reported fairly similar numbers of CJD deaths. However, analysis of individual data showed important between-sources disagreement. Nearly 24% of CJD reported by the mortality register were false-positive diagnoses and 21.6% of the CJD cases diagnosed by the surveillance centre were not registered as CJD in the national mortality statistics. One out of 22 variant CJD cases was not reported as having any type of CJD in the mortality statistics. Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.

Changes of tau profiles in brains of the hamsters infected with scrapie strains 263 K or 139 A possibly associated with the alteration of phosphate kinases

BackgroundPhospho-tau deposition has been described in a rare genetic human prion disease, Gerstmann-Sträussler-Scheinker syndrome, but is not common neuropathological picture for other human and animal transmissible spongiform encephalopathies (TSEs). This study investigated the possible changes of tau and phosphorylated tau (p-tau, at Ser396, Ser404, and Ser202/Thr205) in scrapie experimental animals.MethodsThe profiles of tau and p-tau (p-tau, at Ser396, Ser404, and Ser202/Thr205) in the brain tissues of agents 263K- or 139A-infected hamsters were evaluated by Western blots and real-time PCR. Meanwhile, the transcriptional and expressive levels of GSK3β and CDK5 in the brains were tested.ResultsThe contents of total tau and p-tau at Ser202/Thr205 increased, but p-tau at Ser396 and Ser404 decreased at the terminal stages, regardless of scrapie strains. Transcriptional levels of two tau isoforms were also increased. Additionally, it showed higher CDK5, but lower GSK3β transcriptional and expressive levels in the brains of scrapie-infected animals. Analysis of brain samples collected from different times after inoculated with agent 263 K revealed that the changes of tau profiles and phosphate kinases were time-relative events.ConclusionThese data suggest that changes of profiles of p-tau at Ser396, Ser404 and Ser202/Thr205 are illness-correlative phenomena in TSEs, which may arise of the alteration of phosphate kinases. Alteration of tau, p-tau (Ser396, Ser404, and Ser202/Thr205), GSK3β and CDK5 were either intermediate or consequent events in TSE pathogenesis and proposed the potential linkage of these bioactive proteins with the pathogenesis of prion diseases.

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

Transmissible spongiform encephalopathies such as scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and bovine sporadic encephalopathy in cattle are characterized by the accumulation of a misfolded protein: the pathological prion protein. Ever since bovine sporadic encephalopathy was discovered as the likely cause of the new variant of CJD in humans, parallels between human and animal transmissible spongiform encephalopathies must be viewed under the aspect of a disease risk for humans. In our study we have compared prion characteristics of different forms of sheep scrapie with those of different phenotypes of sporadic CJD. The disease characteristics of sporadic CJD depend considerably on the prion type 1 or 2. Our results show that there are obvious parallels between sporadic CJD type 1 and the so-called atypical/Nor98 scrapie. These parelleles apply to the deposition form of pathological prion protein in the brain, detected by the paraffin-embedded-tissue blot and the prion aggregate stability with regard to denaturation by the chaotropic salt guanidine hydrochloride. The same applies to sporadic CJD type 2 and classical scrapie. The observed parallels between types of sporadic CJD and types of sheep scrapie demonstrate that distinct groups of prion disease exist in different species. This should be taken into consideration when discussing interspecies transmission.

Sporadic Creutzfeldt-Jakob disease: discrete subtypes or a spectrum of disease?

Although the condition we now call sporadic Creutzfeldt–Jakob disease (sCJD) was the first human prion disease to be described, it remains in many important respects the least well understood. In the familial forms of CJD (fCJD) the close association with mutations in the prion protein gene ( PRNP ) limits speculation concerning their aetiology. For the acquired forms of human prion disease (kuru, iatrogenic CJD and variant CJD), we have a good understanding of aetiology in terms of the source of infection and the routes of exposure, and we can model these diseases in experimental animals with a degree of confidence. However, exactly upon what aetiological factors the apparently ‘sporadic’ nature of sCJD depends is open to a number of possible interpretations; and these points of view tend to reflect deep-seated assumptions in the minds of those working on prion diseases or, as they have also been known, the transmissible spongiform encephalopathies. A traditional view of sCJD (often informed by analogies with animal transmissible spongiform encephalopathies and their modelling in mice) tends towards viewing all of these diseases as acquired. In this scenario, sCJD represents cases of human transmissible spongiform encephalopathy for which the human (or animal) source of infection is yet to be determined. By extension, the PRNP mutations associated with familial forms of CJD are proposed to represent susceptibility factors that make infection (presumably by an ubiquitous agent in the environment) and consequent disease almost certain within an individual's lifetime. An alternative view, often favoured by those who subscribe to the prion hypothesis, regards prion protein metabolism as an error prone process. Rarely (and if the incidence of sCJD is a reliable indication, it is a very rare event indeed), the normally benign or positively beneficial cellular prion protein acquires a self-perpetuating abnormal folding state, which ultimately leads to neuronal …

Prions in Milk from Ewes Incubating Natural Scrapie

Since prion infectivity had never been reported in milk, dairy products originating from transmissible spongiform encephalopathy (TSE)-affected ruminant flocks currently enter unrestricted into the animal and human food chain. However, a recently published study brought the first evidence of the presence of prions in mammary secretions from scrapie-affected ewes. Here we report the detection of consistent levels of infectivity in colostrum and milk from sheep incubating natural scrapie, several months prior to clinical onset. Additionally, abnormal PrP was detected, by immunohistochemistry and PET blot, in lacteal ducts and mammary acini. This PrPSc accumulation was detected only in ewes harbouring mammary ectopic lymphoid follicles that developed consequent to Maedi lentivirus infection. However, bioassay revealed that prion infectivity was present in milk and colostrum, not only from ewes with such lympho-proliferative chronic mastitis, but also from those displaying lesion-free mammary glands. In milk and colostrum, infectivity could be recovered in the cellular, cream, and casein-whey fractions. In our samples, using a Tg 338 mouse model, the highest per ml infectious titre measured was found to be equivalent to that contained in 6 µg of a posterior brain stem from a terminally scrapie-affected ewe. These findings indicate that both colostrum and milk from small ruminants incubating TSE could contribute to the animal TSE transmission process, either directly or through the presence of milk-derived material in animal feedstuffs. It also raises some concern with regard to the risk to humans of TSE exposure associated with milk products from ovine and other TSE-susceptible dairy species.

Transmissible spongiform encephalopathies

Abstract Transmissible spongiform encephalopathies (TSEs), or prion diseases, are invariably fatal neurodegenerative diseases of humans and animals. TSEs are believed to be caused by neuronal accumulation of a protease-resistant abnormal conformer of a host-encoded protein known as prion protein. One of the enigmatic properties of TSEs is that they could be both inherited and infectious. TSEs captured worldwide attention after bovine spongiform encephalopathy (BSE, also known as mad cow disease) emerged in Europe and spread to other animals and humans. Cross-species transmission of other animal TSEs was not as clearly documented although scrapie, a centuries-old TSE occurring in sheep, is believed to be the original source of the BSE outbreak.

How Animal Prions Cause Disease in Humans

The transmissible spongiform encephalopathies (TSEs) would seem unlikely candidates for animal disease agents that cross species barriers to cause disease in humans. TSEs are a group of rare but fatal neurodegenerative disorders in which neuronal vacuolation and cell loss within the brain lead to the characteristic spongiform changes, namely holes in the brain, which give the diseases their name. Even within a species, they are notoriously difficult to transmit via oral or other peripheral routes. Usually only transmission via direct inoculation of TSE infectivity into the brain, hardly a natural route of exposure, is very efficient at inducing disease. Additionally, even though the prototypic animal TSE, scrapie in sheep, has been recognized since the 1730s, there has never been any evidence to suggest that sheep scrapie could infect humans and induce a human TSE disease such as Creutzfeldt-Ja-kob disease or Gerstmann-Straussler-Schienker syndrome (Table 1). What, then, has changed to add TSEs to the list of animal diseases which pose a significant threat to human health?

Fibrillization of recombinant bovine prion protein (rec-PrP) in vitro

112 Conversion of normal prion protein ( PrP c ) from the conformation with predominantly α -helical structure into the conformation rich in β -structures ( PrP sc , β -PrP, and PrP res ) underlies the pathogenesis of prion diseases, a special class of degenerative diseases of the nervous system of humans and animals. Prion diseases, or transmissible spongiform encephalopathies (TSEs) of humans, include the Creutzfeldt–Jakob disease (CJD), the Gerstmann–Straussler–Scheinker syndrome, new variant of CJD, kuru, as well as the fatal familial insomnia. The most well-known transmissible spongiform encephalopathies of animals are scrapie of sheep, chronic wasting disease of deer and moose, and bovine spongiform encephalopathy (mad cow disease) [1]. In the course of development of transmissible spongiform encephalopathies, amyloid fibrils (the so-called scrapie-associated fibrils) are formed in brain tissue of both animals and humans. These fibrils consist of β -PrP and are partially resistant to proteolysis. Transmissible spongiform encephalopathies differ in clinical symptoms, neuropathology, neuroanatomical distribution of PrP sc in tissues, and incubation period. It is believed that this heterogeneity of transmissible spongiform encephalopathies is determined by distinctions in the trimeric structure of pathological isoforms of PrP sc [1]. To understand the molecular mechanisms of conversion, the causes of strain differences of causative agents of transmissible spongiform encephalopathies, and interspecies transmission of prion diseases, transformation of recombinant PrP (rec-PrP) of human and different animal species into amyloid fibrils has been performed in vitro in the past years in several laboratories [3–6]. It was shown that the amino acid sequence of PrP markedly affects the formation and morphology of fibrils.

Risk analysis of Transmissible Spongiform Encephalopathies in animals: state-of-the-art

The Bovine Spongiform Encephalopathy (BSE) crisis of the last two decades has shown that proper interaction of risk assessment, risk management and risk communication is essential. Mathematical models and risk assessments have been used as a basis for BSE risk management options and much of the legislation regarding the control and eradication of BSE. Much uncertainty regarding important input parameters remains a major constraint in risk assessment. Uncertainty is one of the most critical and most difficult aspects of communication of risks about Transmissible Spongiform Encephalopathies (TSEs). Nevertheless, the decline in the BSE epidemic in the UK and most European countries demonstrates that management has been, for the most part, successful. Literature pertaining to the three inter-related facets of risk analysis: risk assessment, risk management and risk communication of TSEs of animal origin was reviewed and used to describe the state-of-the-art of risk analysis for TSEs.

Avances en la investigación sobre el prurigo lumbar

The bovine spongiform encephalopathy (BSE) crisis clearly demonstrated the need to keep animal transmissible spongiform encephalopathies (TSE) under control in order to protect animal and human health. Scrapie is the most widespread TSE of livestock in the world. For this reason, health authorities in different countries have elaborated plans that aim towards scrapie eradication. The unusual nature of the scrapie agent and the fragmented status of scientific knowledge about it, along with the limitations of currently available diagnostic tools, make it unlikely that the objective of eradication will be achieved in the near future. Scientific research is focused on acquiring the knowledge that will improve the efficiency of these efforts.