Bovine Spongiform Encephalopathy Research Articles

Market-driven land use in the Legal Amazon

The impact on ecosystems resulting from the introduction of productive activities is a consensus worldwide. However, some analyses have veered away from scientific rigor in favor of other interests. This phenomenon becomes evident when considering productive activities within the Amazon Biome. The diversity in soil structure and vegetation justifies this study and underpins its conclusions. We aimed to assess the impact of livestock farming and soybean cultivation in the state of Mato Grosso, which partially resides within the Amazon Biome. This analysis stems from the promotion of soybean production for animal feed due to the prohibition of meat and bone meal, a regulation that emerged following the Bovine Spongiform Encephalopathy (BSE) event. The results indicate that the prohibition of meat and bone meal in animal feed as a preventive measure against BSE transmission did not influence deforestation in the Legal Amazon in the analyzed region. Similarly, it did not affect the growth of the cattle herd, land income costs, variations in soybean prices in the international market, or beef prices in Brazil. Soybean cultivation did impact deforestation in the Legal Amazon. Government policies related to deforestation were effective in reducing encroachments on the Legal Amazon. Importantly, the most significant expansion of anthropogenic land use occurred within the Cerrado Biome of Mato Grosso rather than within the portion of the Amazon Biome.

Interactions between Cytokines and the Pathogenesis of Prion Diseases: Insights and Implications.

Transmissible Spongiform Encephalopathies (TSEs), including prion diseases such as Bovine Spongiform Encephalopathy (Mad Cow Disease) and variant Creutzfeldt-Jakob Disease, pose unique challenges to the scientific and medical communities due to their infectious nature, neurodegenerative effects, and the absence of a cure. Central to the progression of TSEs is the conversion of the normal cellular prion protein (PrPC) into its infectious scrapie form (PrPSc), leading to neurodegeneration through a complex interplay involving the immune system. This review elucidates the current understanding of the immune response in prion diseases, emphasizing the dual role of the immune system in both propagating and mitigating the disease through mechanisms such as glial activation, cytokine release, and blood-brain barrier dynamics. We highlight the differential cytokine profiles associated with various prion strains and stages of disease, pointing towards the potential for cytokines as biomarkers and therapeutic targets. Immunomodulatory strategies are discussed as promising avenues for mitigating neuroinflammation and delaying disease progression. This comprehensive examination of the immune response in TSEs not only advances our understanding of these enigmatic diseases but also sheds light on broader neuroinflammatory processes, offering hope for future therapeutic interventions.

Exploring carp scales (Cyprinus carpio L.) as a novel source of collagen for dental use: Extraction and characterization

Previous studies have shown that using bovine and pork collagen in dentistry is associated with various limitations, such as bovine spongiform encephalopathy, transmissible spongiform encephalopathy, and foot and mouth disease. This study aims to examine the extraction and characterization of collagen from common carp (Cyprinus carpio L.) scales, as an alternative source in dentistry. The samples used in this study consisted of common carp (C. carpio L.) scales. In the first step, common carp scales were acid-extracted and spray-dried to isolate collagen. After the collagen had been isolated, it was tested for moisture content, ash, acidity, and functional groups, with Indonesian National Standard (SNI) 8076:2014 as the reference standard. The characterization parameters of the common carp scale collagen powder revealed an 11% yield, 3.66% moisture content, 0.32% ash content, and a pH of 7.38. Furthermore, fourier transform infrared spectroscopy spectra confirmed the presence of a triple helix structure. The extraction of collagen from common carp scales using the acetic acid method and spray drying technique successfully adhered to the composition standards specified by the SNI 8076:2014. Based on these findings, common carp scales could be considered a viable collagen replacement source for applications in dentistry.

Time‐varying reaction of U.S. meat demand to animal disease outbreaks

AbstractThis study examined the impact of the mad cow (BSE) and bird flu (HPAI) outbreaks on the demand for beef, pork, and broiler meat in the United States from 1997 to 2022. Using time‐varying elasticities obtained from the Rotterdam model extended to include animal disease outbreaks, we found that the BSE outbreaks significantly reduced beef consumption. These reactions were indeed time‐varying, ranging from 1.312% in 2003 to 1.212% in 2005. HPAI outbreaks had a delayed reaction, with a rebound in broiler meat consumption in the quarter following the start of the outbreak. In general, the magnitude of these reactions was proportional to the severity of an outbreak.

Assessment of the zoonotic potential of atypical scrapie prions in humanized mice reveals rare phenotypic convergence but not identity with sporadic CJD prions.

Atypical/Nor98 scrapie (AS) is an idiopathic infectious prion disease affecting sheep and goats. Recent findings suggest that zoonotic prions from bovine spongiform encephalopathy (C-BSE) may co-propagate with atypical/Nor98 prions in AS sheep brains. Investigating the risk AS poses to humans is crucial. To assess the risk of sheep/goat-to-human transmission of AS, we serially inoculated brain tissue from field and laboratory isolates into transgenic mice overexpressing human prion protein (Met129 allele). We studied clinical outcomes as well as presence of prions in brains and spleens. No transmission occurred on the primary passage, with no clinical disease or pathological prion protein in brains and spleens. On subsequent passages, one isolate gradually adapted, manifesting as prions with a phenotype resembling those causing MM1-type sporadic Creutzfeldt-Jakob disease in humans. However, further characterization using in vivo and in vitro techniques confirmed both prion agents as different strains, revealing a case of phenotypic convergence. Importantly, no C-BSE prions emerged in these mice, especially in the spleen, which is more permissive than the brain for C-BSE cross-species transmission. The results obtained suggest a low the zoonotic for AS. Rare adaptation may allow the emergence of prions phenotypically resembling those spontaneously forming in humans.

A review of the enhanced CJD surveillance feasibility study in the elderly in Scotland, UK

BackgroundVariant Creutzfeldt - Jakob disease (vCJD) arose from dietary contamination with bovine-spongiform-encephalopathy (BSE). Because of concerns that vCJD-cases might be missed in the elderly, a feasibility study of enhanced CJD surveillance on the elderly was begun in 2016. Recruitment was lower than predicted. We describe a review of the challenges encountered in that study: identification, referral, and recruitment, and the effects of actions based on the results of that review.MethodsReview was conducted in 2017. Study data for all eligible cases identified and referred from one participating service (Anne Rowling clinic (ARC)) was curated and anonymised in a bespoke database. A questionnaire was sent out to all the clinicians in medicine of the elderly, psychiatry of old age and neurology (including ARC) specialties in NHS Lothian, exploring possible reasons for low recruitment.ResultsSixty-eight cases were referred from the ARC (March 2016-September 2017): 25% were recruited. Most cases had been referred because of diagnostic uncertainty. No difference was seen between those recruited and the non-recruited, apart from age and referrer. Twelve of 60 participating clinicians completed the questionnaire: only 4 had identified eligible cases. High workload, time constraints, forgetting to refer, unfamiliarity with the eligibility criteria, and the rarity of eligible cases, were some of the reasons given. Suggestions as to how to improve referral of eligible cases included: regular email reminders, feedback to referrers, improving awareness of the study, visible presence of the study team, and integration of the study with other research oriented services. These results were used to increase recruitment but without success.ConclusionRecruitment was lower than predicted. Actions taken following a review at 21 months did not lead to significant improvement; recruitment remained low, with many families/patients declining to take part (75%). In assessing the failure to improve recruitment, two factors need to be considered. Firstly, the initial referral rate was expected to be higher because of existing patients already known to the clinical services, with later referrals being only newly presenting patients. Secondly, the unplanned absence of a dedicated study nurse. Searching digital records/anonymised derivatives to identify eligible patients could be explored.

A validated real-time PCR test for simultaneous detection of Gallus gallus and Meleagris gallopavo in feed instead of an impossible poultry test

Description of the subject. Use of all processed animal proteins (PAPs) in animal feeds was banned in the EU due to the outbreak of bovine spongiform encephalopathy (BSE). This total feed ban was progressively lifted for non-ruminant PAPs from 2013 onwards. Use of ruminant PAPs in feed remains totally prohibited. In order to extend the reintroduction of poultry PAPs in pig feed, and of pig PAPs in poultry feed, as recently decided, poultry species and pig detection tests were required to check that there is no intra-specific recycling. Objectives. In this study, we describe the official EURL-AP real-time PCR method for the simultaneous detection of chicken (Gallus gallus L.) and turkey (Meleagris gallopavo L.), the two most widely used poultry species in PAPs. Method. Classic quality criteria for the validation of a PCR method are considered. A cut-off is required for the interpretation of results. Transferability was tested through an interlaboratory study. Results. The developed PCR assay amplifies an 84 bp fragment encompassing the mitochondrial DNA on 12S ribosomal RNA, tRNA-Val and 16S ribosomal RNA sequences. The qualitative method was successfully assessed for several performance criteria: specificity, sensitivity, efficiency and robustness. The applicability of the test was verified on poultry PAPs and on compound feed containing 0.1% in mass fraction of poultry PAPs. An interlaboratory validation study demonstrated that the proposed real-time PCR method is transferable. Conclusions. The combined chicken-turkey real-time PCR assay is fit for the purpose of detecting poultry PAPs.

Prospective 25-year surveillance of prion diseases in France, 1992 to 2016: a slow waning of epidemics and an increase in observed sporadic forms.

BackgroundPrion diseases are rare, fatal disorders that have repeatedly raised public health concerns since the early 1990s. An active prion disease surveillance network providing national level data was implemented in France in 1992.AimWe aimed to describe the epidemiology of sporadic, genetic and infectious forms of prion diseases in France since surveillance implementation.MethodsWe included all suspected cases notified from January 1992 to December 2016, and cases who died during the period with a definite or probable prion disease diagnosis according to EuroCJD criteria. Demographic, clinical, genetic, neuropathological and biochemical data were collected.ResultsIn total, 25,676 suspected cases were notified and 2,907 were diagnosed as prion diseases, including 2,510 (86%) with sporadic Creutzfeldt-Jakob disease (sCJD), 240 (8%) genetic and 157 (6%) with infectious prion disease. Suspected cases and sCJD cases increased over time. Younger sCJD patients (≤ 50 years) showed phenotypes related to a distinct molecular subtype distribution vs those above 50 years. Compared to other European countries, France has had a higher number of cases with iatrogenic CJD after growth hormone treatment and variant CJD (vCJD) linked to bovine spongiform encephalopathy (second after the United Kingdom), but numbers slowly decreased over time.ConclusionWe observed a decrease of CJD infectious forms, demonstrating the effectiveness of measures to limit human exposure to exogenous prions. However, active surveillance is needed regarding uncertainties about future occurrences of vCJD, possible zoonotic potential of chronic wasting diseases in cervids and increasing trends of sCJD observed in France and other countries.

Monitoring the Sign & Symptoms of Variant Creutzfeldt-Jakob Disease Among Patients with Multiple Myeloma Treated with Ixazomib Capsules in China: A Real-World Pharmacovigilance Survey

Introduction: Variant Creutzfeldt-Jakob disease (vCJD) is a fatal and transmittable neurodegenerative disorder in humans, associated with ingestion of products from Bovine spongiform encephalopathy (BSE) affected cattle. 1 Since April 2018, Ixazomib is approved by National Medical Products Administration (NMPA) for the treatment of multiple myeloma (MM), in China. Before March 2019, the gelatin used for encapsulating ixazomibcapsules was sourced from countries with BSE outbreaks, although all the sources were fully complaint with regulations MM patients were still at risk for BSE, particularly vCJD. Definitive diagnosis of vCJD requires brain biopsy, which is a complex procedure with many complications. World Health Organization (WHO) has indicated a combination of signs and symptoms to assist in defining possible, probable, and definite vCJD cases. 2,3 Here we present phase-2 results from a retrospective analysis, conducted to describe physician-observed signs and symptoms, which may be related to vCJD in MM patients, treated with ixazomibbefore December 2019 in China. Methods: This multi-centre, cross-sectional, web-based survey was conducted in China. Licensed physicians who have prescribed ixazomibcapsules for MM patients before December 2019 and participated in the Phase 1 survey, titled attending or above, specialized in haematology or other related departments and practised in outpatient clinics once a week in the past six months were included. The primary objective was to describe physicians' observed signs and symptoms and the secondary objective was to describe physicians' concerns and awareness of signs and symptoms, which may be related to vCJD in MM patients treated with ixazomib. Eligible physicians completed an online questionnaire with closed-ended multiple-choice questions related to patients' clinical characteristics, responder characteristics, awareness on vCJD-related signs and symptoms, concern on vCJD risk, willingness to prescribe ixazomib in future. Physicians' concern about MM patients who have consumed contaminated ixazomibto get vCJD was measured on a 10-point scale, in which 0 stands for no concern while 10 stands for extremely concerned. Statistical analysis was performed using R, version 3.2 Results: A total of 311 valid questionnaires were received from 318 physicians. The baseline characteristics of respondents are depicted in Table 1. The mean (standard deviation) time of awareness on potential contamination was 19.1 (4.69) months. The average degree of concern decreased from 4.6 in phase 1 to 4.2 in phase 2, as measured on a 10-point scale and willingness to prescribe ixazomibhad increased from 70.1% to 87.8% , after knowing NINLARO ® capsule was sourced (produced before December 2019) from regions with BSE outbreak. A total of 288 respondents reported 1,485 deceased MM patients, who also received ixazomib before 2020. During phase 1, 7 respondents reported 17 patients, who were presented with at least 4 out of 5 prespecified symptoms for potential vCJD. Of which, 2 respondents reported that presented symptoms of 2 patients were caused by vCJD. However, in phase 2, all the 7 respondents have changed their opinion and reported no patient with at least 4 out of 5 prespecified symptoms for potential vCJD, this indicates the possibility of respondents developing better understanding of cVJD after phase 1. Further during phase 2, one respondent reported 2 new living patients presented with at least four of five pre-specified symptoms for potential vCJD and/or ixazomib. On further investigation, the respondent reported the symptoms were not related to vCJD and no tests were performed further to confirm a vCJD diagnosis, possibility of occurrence of these symptoms after phase 1 cannot be ruled out. Additionally, another respondent reported death of a patient that died due to severe diarrhea before reaching hospital. As per respondent, the death may be associated with NINLARO ® and not related to vCJD as the patient was prescribed with ixazomib before December 2019. Conclusion: This study indicates that the risk of vCJD was no longer a concerning factor for physicians and would no longer influence their willingness to prescribe ixazomib.

Development of a sensitive real-time quaking-induced conversion (RT-QuIC) assay for application in prion-infected blood.

Efforts to prevent human-to-human transmission of variant Creutzfeldt-Jakob disease (vCJD) by contaminated blood would be aided by the development of a sensitive diagnostic test that could be routinely used to screen blood donations. As blood samples from vCJD patients are extremely rare, here we describe the optimisation of real-time quaking-induced conversion (RT-QuIC) for detection of PrPSc (misfolded prion protein, a marker of prion infection) in blood samples from an established large animal model of vCJD, sheep experimentally infected with bovine spongiform encephalopathy (BSE). Comparative endpoint titration experiments with RT-QuIC, miniaturized bead protein misfolding cyclic amplification (mb-PMCA) and intracerebral inoculation of a transgenic mouse line expressing sheep PrP (tgOvARQ), demonstrated highly sensitive detection of PrPSc by RT-QuIC in a reference sheep brain homogenate. Upon addition of a capture step with iron oxide beads, the RT-QuIC assay was able to detect PrPSc in whole blood samples from BSE-infected sheep up to two years before disease onset. Both RT-QuIC and mb-PMCA also demonstrated sensitive detection of PrPSc in a reference vCJD-infected human brain homogenate, suggesting that either assay may be suitable for application to human blood samples. Our results support the further development and evaluation of RT-QuIC as a diagnostic or screening test for vCJD.

Industrialization possibilities of purified pig sperm hyaluronidase.

The goals of the present study were to develop a simple method for obtain highly purified pig sperm hyaluronidase (pHyase) and to assess its activity, function, and safety. In mammals, sperm-specific glycophosphatidylinositol (GPI)-anchored Hyase assists sperm penetration through the cumulus mass surrounding the egg and aids in the dispersal of the cumulus-oocyte complex. Recently, Purified bovine sperm hyaluronidase (bHyase) has been shown to enhance therapeutic drug transport by breaking down the hyaluronan barrier to the lymphatic and capillary vessels, thereby facilitating tissue absorption. Commercially available Hyase is typically isolated from bovine or ovine; which have several disadvantages, including the risk of bovine spongiform encephalopathy, low homology with human Hyase, and the requirement for relatively complex isolation procedures. This study successfully isolated highly purified pHyase in only two steps, using ammonium sulfate precipitation and fast protein liquid chromatography. The isolated Hyase had activity equal to that of commercial bHyase, facilitated in vitro fertilization, and effectively dissolved high molecule hyaluronic acid. This simple, effective isolation method could improve the availability of pHyase for research and clinical applications.

Characterization of the First Case of Classical Scrapie in a Sheep in Tunisia

Classical scrapie is a contagious prion disease of sheep and goats. It is endemic in many countries in Europe, North America, and Asia. In Africa, imported scrapie cases have been described in South Africa and Kenia in the past. More recently, several cases have been reported from different regions of Libya, based on clinical signs and histological lesions. Here, we report the results of thorough investigations carried out on a suspect case of scrapie in a 6-year-old Barbarine sheep, born, and bred in Tunisia, showing behavioral changes, weight loss, itching, skin lesions, wool loss, and motor incoordination. Histopathology and immunohistochemistry revealed spongiform change in several brain areas with associated pathological prion protein deposition. Western blotting confirmed the diagnosis and showed a classical scrapie-like molecular pattern of PrPres, different from atypical scrapie and bovine spongiform encephalopathy (BSE) in small ruminants. Sequence analysis of the prion protein gene showed that the animal carried the ARQ/ARQ genotype, one of the most susceptible to classical scrapie. The inoculation of sheep brain homogenate in a susceptible rodent model proved the experimental transmissibility of the disease. These results demonstrate the circulation of classical scrapie in Tunisia and confirm its presence in North Africa, indicating the need to improve epidemiological surveillance and diagnostic capacity for prion diseases in the region.

Experimental transmission of ovine atypical scrapie to cattle

Classical bovine spongiform encephalopathy (BSE) in cattle was caused by the recycling and feeding of meat and bone meal contaminated with a transmissible spongiform encephalopathy (TSE) agent but its origin remains unknown. This study aimed to determine whether atypical scrapie could cause disease in cattle and to compare it with other known TSEs in cattle. Two groups of calves (five and two) were intracerebrally inoculated with atypical scrapie brain homogenate from two sheep with atypical scrapie. Controls were five calves intracerebrally inoculated with saline solution and one non-inoculated animal. Cattle were clinically monitored until clinical end-stage or at least 96 months post-inoculation (mpi). After euthanasia, tissues were collected for TSE diagnosis and potential transgenic mouse bioassay. One animal was culled with BSE-like clinical signs at 48 mpi. The other cattle either developed intercurrent diseases leading to cull or remained clinical unremarkable at study endpoint, including control cattle. None of the animals tested positive for TSEs by Western immunoblot and immunohistochemistry. Bioassay of brain samples from the clinical suspect in Ov-Tg338 and Bov-Tg110 mice was also negative. By contrast, protein misfolding cyclic amplification detected prions in the examined brains from atypical scrapie-challenged cattle, which had a classical BSE-like phenotype. This study demonstrates for the first time that a TSE agent with BSE-like properties can be amplified in cattle inoculated with atypical scrapie brain homogenate.

Detection of classical BSE prions in asymptomatic cows after inoculation with atypical/Nor98 scrapie

The emergence of bovine spongiform encephalopathy (BSE) prions from atypical scrapie has been recently observed upon experimental transmission to rodent and swine models. This study aimed to assess whether the inoculation of atypical scrapie could induce BSE-like disease in cattle. Four calves were intracerebrally challenged with atypical scrapie. Animals were euthanized without clinical signs of prion disease and tested negative for PrPSc accumulation by immunohistochemistry and western blotting. However, an emergence of BSE-like prion seeding activity was detected during in vitro propagation of brain samples from the inoculated animals. These findings suggest that atypical scrapie may represent a potential source of BSE infection in cattle.

Enhanced Creutzfeldt-Jakob disease surveillance in the older population: Assessment of a protocol for screening brain tissue donations for prion disease.

Human prion diseases, including Creutzfeldt-Jakob disease (CJD), occur in sporadic, genetic, and acquired forms. Variant Creutzfeldt-Jakob disease (vCJD) first reported in 1996 in the United Kingdom (UK), resulted from contamination of food with bovine spongiform encephalopathy. There is a concern that UK national surveillance mechanisms might miss some CJD cases (including vCJD), particularly in the older population where other neurodegenerative disorders are more prevalent. We developed a highly sensitive protocol for analysing autopsy brain tissue for the misfolded prion protein (PrPSc ) associated with prion disease, which could be used to screen for prion disease in the elderly. Brain tissue samples from 331 donors to the Edinburgh Brain and Tissue Bank (EBTB), from 2005 to 2022, were analysed, using immunohistochemical analysis on fixed tissue, and five biochemical tests on frozen specimens from six brain regions, based on different principles for detecting PrPSc . An algorithm was established for classifying the biochemical results. To test the effectiveness of the protocol, several neuropathologically confirmed prion disease controls, including vCJD, were included and blinded in the study cohort. On unblinding, all the positive control cases had been correctly identified. No other cases tested positive; our analysis uncovered no overlooked prion disease cases. Our algorithm for classifying cases was effective for handling anomalous biochemical results. An overall analysis suggested that a reduced biochemical protocol employing only three of the five tests on only two brain tissue regions gave sufficient sensitivity and specificity. We conclude that this protocol may be useful as a UK-wide screening programme for human prion disease in selected brains from autopsies in the elderly. Further improvements to the protocol were suggested by enhancements of the in vitro conversion assays made during the course of this study.

Meat industry by-products: a bio-refinery approach to the production of safe, value added products for sustainable agriculture applications

This mini-review review examines the role of animal by-products (ABP), produced by the process known as rendering. It explains how the use of rendered products has evolved and changed over the last 50 years and how the bovine spongiform encephalopathy (BSE) epidemic in the UK and the rest of Europe challenged the survival of the industry. The subsequent changes to the rendering industry resulting from BSE are described by way of key research and regulatory changes. As a result of the developments in the modern rendering industry, it has evolved into an important component of the current human food chain. The role of the rendering industry in producing a wide range of safe, high quality, sustainable products from ABP materials is explored.

Inducing prion protein shedding as a neuroprotective and regenerative approach in pathological conditions of the brain: from theory to facts.

In the last decades, the role of the prion protein (PrP) in neurodegenerative diseases has been intensively investigated, initially in prion diseases of humans (e.g., Creutzfeldt-Jakob disease) and animals (e.g., scrapie in sheep, chronic wasting disease in deer and elk, or "mad cow disease" in cattle). Templated misfolding of physiological cellular prion protein (PrPC) into an aggregation-prone isoform (termed PrP "Scrapie" (PrPSc)), self-replication and spreading of the latter inside the brain and to peripheral tissues, and the associated formation of infectious proteopathic seeds (termed "prions") are among the essential pathogenic mechanisms underlying this group of fatal and transmissible spongiform encephalopathies. Later, key roles of the correctly folded PrPC were identified in more common human brain diseases (such as Alzheimer's disease or Parkinson's disease) associated with the misfolding and/or accumulation of other proteins (such as amyloid-β, tau or α-synuclein, respectively). PrPC has also been linked with neuroprotective and regenerative functions, for instance in hypoxic/ischemic conditions such as stroke. However, despite a mixed "bouquet" of suggested functions, our understanding of pathological and, especially, physiological roles played by PrPC in the brain and beyond is certainly incomplete. Interactions with various other proteins at the cell surface or within intracellular compartments may account for the functional diversity linked with PrPC. Moreover, conserved endogenous proteolytic processing of PrPC generates several defined PrPC fragments, possibly holding intrinsic functions in physiological and pathological conditions, thus making the "true and complete biology" of this protein more complicated to be elucidated. Here, we focus on one of those released PrPC fragments, namely shed PrP (sPrP), generated by a membrane-proximate ADAM10-mediated cleavage event at the cell surface. Similar to other soluble PrPC fragments (such as the N1 fragment representing PrP's released N-terminal tail upon the major α-cleavage event) or experimentally employed recombinant PrP, sPrP is being suggested to act neuroprotective in Alzheimer's disease and other protein misfolding diseases. Several lines of evidence on extracellular PrPC (fragments) suggest that induction of PrPC release could be a future therapeutic option in various brain disorders. Our recent identification of a substrate-specific approach to stimulate the shedding by ADAM10, based on ligands binding to cell surface PrPC, may further set the stage for research into this direction.

Efficacy of Wex-cide 128 disinfectant against multiple prion strains.

Prion diseases are transmissible, fatal neurologic diseases that include Creutzfeldt-Jakob Disease (CJD) in humans, chronic wasting disease (CWD) in cervids, bovine spongiform encephalopathy (BSE) in cattle and scrapie in sheep. Prions are extremely difficult to inactivate and established methods to reduce prion infectivity are often dangerous, caustic, expensive, or impractical. Identifying viable and safe methods for treating prion contaminated materials is important for hospitals, research facilities, biologists, hunters, and meat-processors. For three decades, some prion researchers have used a phenolic product called Environ LpH (eLpH) to inactivate prions. ELpH has been discontinued, but a similar product, Wex-cide 128, containing the similar phenolic chemicals as eLpH is now available. In the current study, we directly compared the anti-prion efficacy of eLpH and Wex-cide 128 against prions from four different species (hamster 263K, cervid CWD, mouse 22L and human CJD). Decontamination was performed on either prion infected brain homogenates or prion contaminated steel wires and mouse bioassay was used to quantify the remaining prion infectivity. Our data show that both eLpH and Wex-cide 128 removed 4.0-5.5 logs of prion infectivity from 22L, CWD and 263K prion homogenates, but only about 1.25-1.50 logs of prion infectivity from human sporadic CJD. Wex-cide 128 is a viable substitute for inactivation of most prions from most species, but the resistance of CJD to phenolic inactivation is a concern and emphasizes the fact that inactivation methods should be confirmed for each target prion strain.

The Impact of Animal Disease Outbreaks on China’s Meat Imports

ABSTRACT We assess the effect of three animal disease outbreaks on China’s meat imports from 1992 to 2017, namely foot-and-mouth disease (FMD) for swine, bovine spongiform encephalopathy (BSE) for cattle, and highly pathogenic avian influenza (HPAI) for poultry. Using system-GMM and FGLS estimators, we find that outbreaks of animal diseases in exporting countries reduce China’s import of the meat products. Additionally, we find positive trade diversion and substitution effects in both FMD and HPAI but negative effects in BSE. Although these results indicate that China can accommodate its meat consumption needs through international trade now, we are skeptical that it can continue to do so if animal husbandry practices do not improve in China. This calls for major meat exporters to improve production efficiency and reduce the prevalence of animal diseases. With increasing environmental pressure and high dependency on imported feed caused by the expanding livestock sector, we recommend a sustainable diet by encouraging less consumption of meat.

Conservation of vCJD Strain Properties After Extraction and In Vitro Propagation of PrPSc from Archived Formalin-Fixed Brain and Appendix Tissues Using Highly Sensitive Protein Misfolding Cyclic Amplification.

Three retrospective lymphoreticular tissue studies (Appendix I, II, and III) aimed to estimate the UK prevalence of variant Creutzfeldt-Jakob disease (vCJD), following exposure of the population to the bovine spongiform encephalopathy (BSE) agent, in the late 1980s and 1990s. These studies evaluated the presence of abnormal prion protein aggregates, in archived formalin-fixed paraffin-embedded (FFPE) appendectomy samples, by immunohistochemical detection. Although there was concordance in the estimated prevalence of vCJD from these studies, the identification of positive specimens from pre- and post-BSE-exposure periods in Appendix III study has raised questions regarding the nature and origin of the detected abnormal prion protein. We applied a robust and novel approach in the extraction of disease-associated prion protein (PrPSc) present in frozen and FFPE samples of brain and appendix from a patient with pathologically confirmed vCJD. The extracted material was used to seed the highly sensitive protein misfolding cyclic amplification assay (hsPMCA) to investigate the in vitro and in vivo propagation properties of the extracted abnormal prion protein. We demonstrate that PrPSc can be successfully extracted from FFPE appendix tissue and propagated in vitro. Bioassay in wild-type and gene-targeted mouse models confirmed that the extracted and amplified product is infectious and retains strain properties consistent with vCJD. This provides a highly sensitive and reliable platform for subsequent analysis of the archived FFPE appendix tissue derived from the Appendix II and III surveys, to further evaluate the nature of the abnormal PrP detected in the positive samples.