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Sample records for animal transmissible spongiform

  1. Pathobiology and diagnosis of animal transmissible spongiform encephalopathies: current knowledge, research gaps, and opportunities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transmissible spongiform encephalopathies (TSEs) are fatal neurologic diseases that can affect several animal species and human beings. There are four animal TSE agents found in the United States: scrapie of sheep and goats; chronic wasting disease (CWD) of deer, elk, and moose; transmissible mink ...

  2. Medicinal and other products and human and animal transmissible spongiform encephalopathies: memorandum from a WHO meeting.

    PubMed Central

    1997-01-01

    The report in March 1996 of 10 human cases of a novel from of Creutzfeldt-Jakob disease in the United Kingdom, and its possible link to the agent that causes bovine spongiform encephalopathy (BSE), raises many questions about the safety of animal-derived products and by-products entering the food chain or being used in medicine. This Memorandum updates the preventive measures put forward in 1991 to minimize the risks associated with the use of bovine-derived materials in medicinal products and medical devices. PMID:9509622

  3. Transmissible Spongiform Encephalopathy and Meat Safety

    NASA Astrophysics Data System (ADS)

    Ward, Hester J. T.; Knight, Richard S. G.

    Prion diseases or transmissible spongiform encephalopathies (TSEs) comprise a wide-ranging group of neurodegenerative diseases found in animals and humans. They have diverse causes and geographical distributions, but have similar pathological features, transmissibility and, are ultimately, fatal. Central to all TSEs is the presence of an abnormal form of a normal host protein, namely the prion protein. Because of their potential transmissibility, these diseases have wide public health ramifications.

  4. The transmissible spongiform encephalopathies of livestock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal protein misfolding neurodegenerative diseases. TSEs have been described in several species including bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, tr...

  5. Experimental Interspecies Transmission Studies of the Transmissible Spongiform Encephalopathies to Cattle: Comparison to Bovine Spongiform Encephalopathy in Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases or transmissible spongiform encephalopathies (TSEs) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (TME); chronic wasting disease (CWD) of deer, elk and moose; and bovine spongiform encephalopathy (BSE) of cattle. Since the emergence of BSE and its pr...

  6. Fundamental immunological problems associated with "transmissible spongiform encephalopathies".

    PubMed

    Ebringer, Alan; Rashid, Taha; Wilson, Clyde

    2015-02-01

    "Bovine spongiform encephalopathy", "scrapie", as well as Creutzfeldt-Jakob disease and kuru belong to a group of related neurological conditions termed "transmissible spongiform encephalopathies". These diseases are based on the LD50 measurement whereby saline brain homogenates are injected into experimental animals and when 50% of them develop symptoms, this is considered as transmission of the disease, but the gold standard for diagnosis is autopsy examination. However, an untenable assumption is being made in that saline brain homogenates do not cause tissue damage but it is known since the time of Pasteur, that they give rise to "post-rabies vaccination allergic encephalomyelitis". This is the fundamental flaw in the diagnosis of these diseases. A way forward, however, is to examine infectious agents, such as Acinetobacter which show molecular mimicry with myelin and elevated levels of antibodies to this microbe are found in multiple sclerosis patients and animals affected by "bovine spongiform encephalopathy". PMID:25573495

  7. The transmissible spongiform encephalopathies of livestock.

    PubMed

    Greenlee, Justin J; Greenlee, M Heather West

    2015-01-01

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal protein-misfolding neurodegenerative diseases. TSEs have been described in several species, including bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, transmissible mink encephalopathy (TME) in mink, and Kuru and Creutzfeldt-Jakob disease (CJD) in humans. These diseases are associated with the accumulation of a protease-resistant, disease-associated isoform of the prion protein (called PrP(Sc)) in the central nervous system and other tissues, depending on the host species. Typically, TSEs are acquired through exposure to infectious material, but inherited and spontaneous TSEs also occur. All TSEs share pathologic features and infectious mechanisms but have distinct differences in transmission and epidemiology due to host factors and strain differences encoded within the structure of the misfolded prion protein. The possibility that BSE can be transmitted to humans as the cause of variant Creutzfeldt-Jakob disease has brought attention to this family of diseases. This review is focused on the TSEs of livestock: bovine spongiform encephalopathy in cattle and scrapie in sheep and goats. PMID:25991695

  8. Public health issues related to animal and human spongiform encephalopathies: memorandum from a WHO meeting.

    PubMed Central

    1992-01-01

    The transmissible spongiform encephalopathies (TSE) include bovine spongiform encephalopathy (BSE), which was first described in 1986 in the United Kingdom but has occurred subsequently in several other countries. This Memorandum reviews the existing state of knowledge on all the known spongiform encephalopathies, and evaluates the pathways of transmission and associated hazards. The possible implications of the animal diseases, especially BSE, with regard to the use of animal tissues as animal feed, human food, and in the preparation of medicinal and other products for human use are discussed, with recommendations to national health authorities on appropriate measures to minimize the consequences of BSE to public and animal health. PMID:1600580

  9. Transmission of sheep-bovine spongiform encephalopathy to pigs.

    PubMed

    Hedman, Carlos; Bolea, Rosa; Marín, Belén; Cobrière, Fabien; Filali, Hicham; Vazquez, Francisco; Pitarch, José Luis; Vargas, Antonia; Acín, Cristina; Moreno, Bernardino; Pumarola, Martí; Andreoletti, Olivier; Badiola, Juan José

    2016-01-01

    Experimental transmission of the bovine spongiform encephalopathy (BSE) agent has been successfully reported in pigs inoculated via three simultaneous distinct routes (intracerebral, intraperitoneal and intravenous). Sheep derived BSE (Sh-BSE) is transmitted more efficiently than the original cattle-BSE isolate in a transgenic mouse model expressing porcine prion protein. However, the neuropathology and distribution of Sh-BSE in pigs as natural hosts, and susceptibility to this agent, is unknown. In the present study, seven pigs were intracerebrally inoculated with Sh-BSE prions. One pig was euthanized for analysis in the preclinical disease stage. The remaining six pigs developed neurological signs and histopathology revealed severe spongiform changes accompanied by astrogliosis and microgliosis throughout the central nervous system. Intracellular and neuropil-associated pathological prion protein (PrP(Sc)) deposition was consistently observed in different brain sections and corroborated by Western blot. PrP(Sc) was detected by immunohistochemistry and enzyme immunoassay in the following tissues in at least one animal: lymphoid tissues, peripheral nerves, gastrointestinal tract, skeletal muscle, adrenal gland and pancreas. PrP(Sc) deposition was revealed by immunohistochemistry alone in the retina, optic nerve and kidney. These results demonstrate the efficient transmission of Sh-BSE in pigs and show for the first time that in this species propagation of bovine PrP(Sc) in a wide range of peripheral tissues is possible. These results provide important insight into the distribution and detection of prions in non-ruminant animals. PMID:26742788

  10. Progress on low susceptibility mechanisms of transmissible spongiform encephalopathies

    PubMed Central

    QING, Li-Li; ZHAO, Hui; LIU, Lin-Lin

    2014-01-01

    Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of fatal neurodegenerative diseases detected in a wide range of mammalian species. The “protein-only” hypothesis of TSE suggests that prions are transmissible particles devoid of nucleic acid and the primary pathogenic event is thought to be the conversion of cellular prion protein (PrPC) into the disease-associated isoform (PrPSc). According to susceptibility to TSEs, animals can be classified into susceptible species and low susceptibility species. In this review we focus on several species with low susceptibility to TSEs: dogs, rabbits, horses and buffaloes. We summarize recent studies into the characteristics of low susceptibility regarding protein structure, and biochemical and genetic properties. PMID:25297084

  11. Excretion of Transmissible Spongiform Encephalopathy Infectivity in Urine

    PubMed Central

    Gregori, Luisa; Kovacs, Gabor G.; Alexeeva, Irina; Budka, Herbert

    2008-01-01

    The route of transmission of most naturally acquired transmissible spongiform encephalopathy (TSE) infections remains speculative. To investigate urine as a potential source of TSE exposure, we used a sensitive method for detection and quantitation of TSE infectivity. Pooled urine collected from 22 hamsters showing clinical signs of 263K scrapie contained 3.8 ± 0.9 infectious doses/mL of infectivity. Titration of homogenates of kidneys and urinary bladders from the same animals gave concentrations 20,000-fold greater. Histologic and immunohistochemical examination of these same tissues showed no indications of inflammatory or other pathologic changes except for occasional deposits of disease-associated prion protein in kidneys. Although the source of TSE infectivity in urine remains unresolved, these results establish that TSE infectivity is excreted in urine and may thereby play a role in the horizontal transmission of natural TSEs. The results also indicate potential risk for TSE transmission from human urine–derived hormones and other medicines. PMID:18760007

  12. Molecular aspects of disease pathogenesis in the transmissible spongiform encephalopathies.

    PubMed

    Priola, Suzette A; Vorberg, Ina

    2004-01-01

    The transmissible spongiform encephalopathy (TSE) diseases are a group of rare, fatal, and transmissible neurodegenerative diseases that include kuru and Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep, transmissible mink encephalopathy (TME), and chronic wasting disease (CWD) in mule deer and elk. Over the last 20 yr, they have gone from a fascinating but relatively obscure group of diseases to one that is a major agricultural and economic problem as well as a threat to human health. The shift in the relative impact of the TSE diseases began in the late 1970s when the United Kingdom altered the process by which animal carcasses were rendered to provide a protein supplement (i.e., meat and bone meal) to sheep, cattle, and other livestock. Several years later a new disease was recognized in the British cattle population. The pathological and immunohistochemical characteristics of the disease clearly placed it among the TSEs. The new disease was named bovine spongiform encephalopathy (BSE) by the scientific community and "mad cow disease" by the less-than-scientific press. At its peak in the UK, several thousand cattle a year were diagnosed with BSE, and millions of cattle were slaughtered. Introduction of the specified offals ban as well as banning the practice of feeding ruminants to other ruminants has led to a drastic decrease in the number of yearly BSE cases in the UK (less than 500 in 2003), and the epidemic is clearly on the wane. However, BSE has now spread throughout the rest of Europe, as well as to Japan, Russia, Canada, and Israel and thus remains a worldwide problem.A primary concern following the identification of BSE in 1985 was that it might cross species barriers to infect humans. Initially, it was thought that transmission of BSE to humans was unlikely, given that humans appeared to be resistant to scrapie, an animal TSE that had been endemic in British sheep for centuries. However, a few years after BSE was first recognized, a

  13. Laboratory activities involving transmissible spongiform encephalopathy causing agents

    PubMed Central

    Leunda, Amaya; Van Vaerenbergh, Bernadette; Baldo, Aline; Roels, Stefan; Herman, Philippe

    2013-01-01

    Since the appearance in 1986 of epidemic of bovine spongiform encephalopathy (BSE), a new form of neurological disease in cattle which also affected human beings, many diagnostic and research activities have been performed to develop detection and therapeutic tools. A lot of progress was made in better identifying, understanding and controlling the spread of the disease by appropriate monitoring and control programs in European countries. This paper reviews the recent knowledge on pathogenesis, transmission and persistence outside the host of prion, the causative agent of transmissible spongiform encephalopathies (TSE) in mammals with a particular focus on risk (re)assessment and management of biosafety measures to be implemented in diagnostic and research laboratories in Belgium. Also, in response to the need of an increasing number of European diagnostic laboratories stopping TSE diagnosis due to a decreasing number of TSE cases reported in the last years, decontamination procedures and a protocol for decommissioning TSE diagnostic laboratories is proposed. PMID:24055928

  14. Bovine Spongiform Encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE), also referred to as “mad cow disease” is a chronic, non-febrile, neuro-degenerative disease affecting the central nervous system. The transmissible spongiform encephalopathies (TSEs) of domestic animals, of which BSE is a member includes scrapie of sheep...

  15. Public risk perception of relaxation of transmissible spongiform encephalopathies (TSE) measures in Europe.

    PubMed

    Dressel, K; Perazzini, A; Ru, G; Van Wassenhove, W

    2011-01-01

    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. PMID:22043919

  16. A potential role for transmissible spongiform encephalopathies in Neanderthal extinction.

    PubMed

    Underdown, Simon

    2008-01-01

    The Neanderthals were a Eurasian human species of the genus Homo that disappeared approximately 30,000 years ago. The cause or causes of their extinction continues to intrigue specialists and non-specialists alike. Here a contributory role for Transmissible Spongiform Encephalopathies (TSEs) is suggested. TSEs could have infected Neanderthal groups as a result of general cannibalistic activity and brain tissue consumption in particular. Further infection could then have taken place through continued cannibalistic activity or via shared used of infected stone tools. A modern human hunter-gatherer proxy has been developed and applied as a hypothetical model to the Neanderthals. This hypothesis suggests that the impact of TSEs on the Neanderthals could have been dramatic and have played a large part in contributing to the processes of Neanderthal extinction. PMID:18280671

  17. Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transmissible Spongiform Encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in cervids, and bovine spongiform encephalopathy (BSE), are fatal diseases of the nervous system associated with accumulation of misfolded prion protein (PrPSc). Different strains of BSE exist...

  18. Assessing transmissible spongiform encephalopathy species barriers with an in vitro prion protein conversion assay.

    PubMed

    Johnson, Christopher J; Carlson, Christina M; Morawski, Aaron R; Manthei, Alyson; Cashman, Neil R

    2015-01-01

    Studies to understanding interspecies transmission of transmissible spongiform encephalopathies (TSEs, prion diseases) are challenging in that they typically rely upon lengthy and costly in vivo animal challenge studies. A number of in vitro assays have been developed to aid in measuring prion species barriers, thereby reducing animal use and providing quicker results than animal bioassays. Here, we present the protocol for a rapid in vitro prion conversion assay called the conversion efficiency ratio (CER) assay. In this assay cellular prion protein (PrPC) from an uninfected host brain is denatured at both pH 7.4 and 3.5 to produce two substrates. When the pH 7.4 substrate is incubated with TSE agent, the amount of PrPC that converts to a proteinase K (PK)-resistant state is modulated by the original host's species barrier to the TSE agent. In contrast, PrPC in the pH 3.5 substrate is misfolded by any TSE agent. By comparing the amount of PK-resistant prion protein in the two substrates, an assessment of the host's species barrier can be made. We show that the CER assay correctly predicts known prion species barriers of laboratory mice and, as an example, show some preliminary results suggesting that bobcats (Lynx rufus) may be susceptible to white-tailed deer (Odocoileus virginianus) chronic wasting disease agent. PMID:25867521

  19. Assessing transmissible spongiform encephalopathy species barriers with an in vitro prion protein conversion assay

    USGS Publications Warehouse

    Johnson, Christopher J.; Carlson, Christina M.; Morawski, Aaron R.; Manthei, Alyson; Cashman, Neil R.

    2015-01-01

    Studies to understanding interspecies transmission of transmissible spongiform encephalopathies (TSEs, prion diseases) are challenging in that they typically rely upon lengthy and costly in vivo animal challenge studies. A number of in vitro assays have been developed to aid in measuring prion species barriers, thereby reducing animal use and providing quicker results than animal bioassays. Here, we present the protocol for a rapid in vitroprion conversion assay called the conversion efficiency ratio (CER) assay. In this assay cellular prion protein (PrPC) from an uninfected host brain is denatured at both pH 7.4 and 3.5 to produce two substrates. When the pH 7.4 substrate is incubated with TSE agent, the amount of PrPC that converts to a proteinase K (PK)-resistant state is modulated by the original host’s species barrier to the TSE agent. In contrast, PrPC in the pH 3.5 substrate is misfolded by any TSE agent. By comparing the amount of PK-resistant prion protein in the two substrates, an assessment of the host’s species barrier can be made. We show that the CER assay correctly predicts known prion species barriers of laboratory mice and, as an example, show some preliminary results suggesting that bobcats (Lynx rufus) may be susceptible to white-tailed deer (Odocoileus virginianus) chronic wasting disease agent.

  20. Bovine Spongiform Encephalopathy: Atypical Pros and Cons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transmissible spongiform encephalopathies (TSEs) are fatal neurologic diseases that affect several mammalian species including human beings. Four animal TSE agents have been reported: scrapie of sheep and goats; chronic wasting disease (CWD) of deer, elk, and moose; transmissible mink encephalopath...

  1. 76 FR 38667 - Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-01

    ... blood and blood products and human cells, tissues and cellular and tissue-based products. FDA intends to... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Transmissible Spongiform Encephalopathies Advisory...

  2. Transmissible spongiform encephalopathies (TSE): minimizing the risk of transmission by biological/biopharmaceutical products: an industry perspective.

    PubMed

    Kozak, R W; Golker, C F; Stadler, P

    1996-01-01

    Several guidelines and recommendations have been published on assessing the potential risk of a biological product being contaminated with an agent causing a Transmissible Spongiform Encephalopathy (TSE). Basic principles which can be used during the manufacturing of biological products to minimize the risk of transmission of TSE agents include the following: (i) obtaining animals, tissues or animal-derived raw materials from countries in which the relevant TSE agent is reported to be absent; (ii) screening animal-derived material for appropriate animal husbandry, feeding practices, health certification, tissue procurement and processing practices, and human-derived material for appropriate medical history information and, if relevant, plasma donor exclusion criteria; (iii) selection of tissue source of raw material with reference to potential risk for harbouring or amplifying TSE agents; (IV) human tropism of TSE agent of concern; (v) quantity of raw material used to manufacture a dose of product; (vi) number of daily doses required for indication; (vii) route of administration; (viii) indication and age of patient; and (ix) clearance capabilities by the product purification scheme. A risk evaluation will be represented for Trasylol (Aprotinin) which is manufactured from bovine lung tissue. Trasylol is a protease inhibitor used in the control of blood loss during open heart surgery. Bovine Spongiform Encephalopathy (BSE) is a concern when a product is derived from a bovine source. Even though only bovine lung tissue from BSE-free countries is used to manufacture Trasylol, it was decided, based on the primary tissue source selection, to evaluate the potential of the purification process to clear a TSE agent. Duplicate "spiking experiments" were performed using a mouse-adapted strain of scrapie as the model for BSE. Four steps in the purification process were evaluated. Titration of "spiked" loading material and output samples was performed at dilutions of 10(-4) to

  3. Identification of a heritable polymorphism in the bovine prion gene associated with genetic transmissible spongiform encephalopathy: evidence of heritable BSE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) of cattle. Classical BSE is associated with ingestion of BSE-contaminated feedstuffs. H- and L-type BSE, collectively known as atypical BSE, differ from classical BSE by displaying a different di...

  4. Identification of a heritable polymorphism in bovine PRNP associated with genetic transmissible spongiform encephalopathy: evidence of heritable BSE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) of cattle. Classical BSE is associated with ingestion of BSE-contaminated feedstuffs. H- and L-type BSE, collectively known as atypical BSE, differ from classical BSE by displaying a different disease phenoty...

  5. Transmissible spongiform encephalopathies: a family of etiologically complex diseases--a review.

    PubMed

    Bounias, Michel; Purdey, Mark

    2002-10-01

    The upsurge of 'mad cow disease' with its human implications has raised the problem of the etiological mechanisms and the similarities or differences underlying the family of transmissible spongiform encephalopathies. Structural properties of prions are reviewed in connection with their natural distribution and functions, factors of transmissibility and mechanisms of pathogenicity. Polymorphism is examined in relation to disease phenotype variants. The role of oxidative factors is emphasized, while raising complexity about the role of copper ions. Further investigation directions are suggested. PMID:12389776

  6. Defining and Assessing Analytical Performance Criteria for Transmissible Spongiform Encephalopathy-Detecting Amyloid Seeding Assays.

    PubMed

    Gray, John G; Graham, Catherine; Dudas, Sandor; Paxman, Eric; Vuong, Ben; Czub, Stefanie

    2016-05-01

    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, in vitro; 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. In vitro 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 in vitro 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 in vitro PrP conversion may be used to titrate TSE infectivity, and, as a result, provide a comprehensive extrapolation of analytical sensitivity differences between bioassay, TSE rapid tests, and in vitro PrP conversion for elk CWD. PMID:27068712

  7. Studies of the transmissibility of the agent of bovine spongiform encephalopathy to the domestic chicken

    PubMed Central

    2011-01-01

    Background Transmission of the prion disease bovine spongiform encephalopathy (BSE) occurred accidentally to cattle and several other mammalian species via feed supplemented with meat and bone meal contaminated with infected bovine tissue. Prior to United Kingdom controls in 1996 on the feeding of mammalian meat and bone meal to farmed animals, the domestic chicken was potentially exposed to feed contaminated with the causal agent of BSE. Although confirmed prion diseases are unrecorded in avian species a study was undertaken to transmit BSE to the domestic chicken by parenteral and oral inoculations. Transmissibility was assessed by clinical monitoring, histopathological examinations, detection of a putative disease form of an avian prion protein (PrP) in recipient tissues and by mouse bioassay of tissues. Occurrence of a progressive neurological syndrome in the primary transmission study was investigated by sub-passage experiments. Results No clinical, pathological or bioassay evidence of transmission of BSE to the chicken was obtained in the primary or sub-passage experiments. Survival data showed no significant differences between control and treatment groups. Neurological signs observed, not previously described in the domestic chicken, were not associated with significant pathology. The diagnostic techniques applied failed to detect a disease associated form of PrP. Conclusion Important from a risk assessment perspective, the present study has established that the domestic chicken does not develop a prion disease after large parenteral exposures to the BSE agent or after oral exposures equivalent to previous exposures via commercial diets. Future investigations into the potential susceptibility of avian species to mammalian prion diseases require species-specific immunochemical techniques and more refined experimental models. PMID:22093239

  8. In vitro prion protein conversion suggests risk of bighorn sheep (Ovis canadensis) to transmissible spongiform encephalopathies

    USGS Publications Warehouse

    Johnson, Christopher J.; Morawski, A.R.; Carlson, C.M.; Chang, H.

    2013-01-01

    Background: Transmissible spongiform encephalopathies (TSEs) affect both domestic sheep (scrapie) and captive and free-ranging cervids (chronic wasting disease; CWD). The geographical range of bighorn sheep (Ovis canadensis; BHS) overlaps with states or provinces that have contained scrapie-positive sheep or goats and areas with present epizootics of CWD in cervids. No TSEs have been documented in BHS, but the susceptibility of this species to TSEs remains unknown. Results: We acquired a library of BHS tissues and found no evidence of preexisting TSEs in these animals. The prion protein gene (Prnp) in all BHS in our library was identical to scrapie-susceptible domestic sheep (A136R 154Q171). Using an in vitro prion protein conversion assay, which has been previously used to assess TSE species barriers and, in our study appears to recollect known species barriers in mice, we assessed the potential transmissibility of TSEs to BHS. As expected based upon Prnp genotype, we observed BHS prion protein conversion by classical scrapie agent and evidence for a species barrier between transmissible mink encephalopathy (TME) and BHS. Interestingly, our data suggest that the species barrier of BHS to white-tailed deer or wapiti CWD agents is likely low. We also used protein misfolding cyclic amplification to confirm that CWD, but not TME, can template prion protein misfolding in A136R 154Q171genotype sheep. Conclusions: Our results indicate the in vitro conversion assay used in our study does mimic the species barrier of mice to the TSE agents that we tested. Based on Prnp genotype and results from conversion assays, BHS are likely to be susceptible to infection by classical scrapie. Despite mismatches in amino acids thought to modulate prion protein conversion, our data indicate that A136R154Q171 genotype sheep prion protein is misfolded by CWD agent, suggesting that these animals could be susceptible to CWD. Further investigation of TSE transmissibility to BHS, including

  9. Epidemiological observations on spongiform encephalopathies in captive wild animals in the British Isles.

    PubMed

    Kirkwood, J K; Cunningham, A A

    1994-09-24

    Since 1986, scrapie-like spongiform encephalopathy has been diagnosed in 19 captive wild animals of eight species at or from eight zoological collections in the British Isles. The affected animals have comprised members of the family Bovidae: one nyala (Tragelaphus angasi), four eland (Taurotragus oryx), and six greater kudu (Tragelaphus strepsiceros), one gemsbok (Oryx gazella), one Arabian oryx (Oryx leucoryx), and one scimitar-horned oryx (Oryx dammah), and members of the family Felidae: four cheetah (Acinonyx jubatus) and one puma (Felis concolor). In addition, three cases of a spongiform encephalopathy of unknown aetiology have been reported in ostriches (Struthio camellus) from two zoos in north west Germany. Three features suggest that some of these cases may have been caused by the agent of bovine spongiform encephalopathy (BSE). First, they have been temporally and geographically coincident with the BSE epidemic. Secondly, in all the ungulates for which details are available, it is possible that either the affected animal itself, or the herd into which it was born or moved, had been exposed to proprietary feeds containing ruminant-derived protein or other potentially contaminated material, and all the carnivores had been fed parts of cattle carcases judged unfit for human consumption. Thirdly, the pathological results of inoculating mice with a homogenate of fixed brain tissue from the nyala and from one greater kudu were similar to the results of inoculating mice with BSE brain tissue. PMID:7817514

  10. The prion diseases of animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that affect several species of animals and include bovine spongiform encephalopathy (BSE), scrapie in sheep and goats, chronic wasting disease (CWD) in cervids, and transmissible mink encephalopat...

  11. Prion Diseases: Update on Mad Cow Disease, Variant Creutzfeldt-Jakob Disease, and the Transmissible Spongiform Encephalopathies.

    PubMed

    Janka, Jacqueline; Maldarelli, Frank

    2004-08-01

    Transmissible spongiform encephalopathies (TSEs) are a group of progressive, fatal neurodegenerative disorders that share a common spongiform histopathology. TSEs may be transmitted in a sporadic, familial, iatrogenic, or zoonotic fashion. The putative infectious agent of TSE, the prion, represents a novel paradigm of infectious disease with disease transmission in the absence of nucleic acid. Several small but spectacular epidemics of TSEs in man have prompted widespread public health and food safety concerns. Although TSEs affect a comparatively small number of individuals, prion research has revealed fascinating insights of direct relevance to common illnesses. This paper reviews recent advances that have shed new light on the nature of prions and TSEs. PMID:15265460

  12. Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control.

    PubMed

    Seuberlich, Torsten; Heim, Dagmar; Zurbriggen, Andreas

    2010-11-01

    Since 1987, when bovine spongiform encephalopathy (BSE) emerged as a novel disease in cattle, enormous efforts were undertaken to monitor and control the disease in ruminants worldwide. The driving force was its high economic impact, which resulted from trade restrictions and the loss of consumer confidence in beef products, the latter because BSE turned out to be a fatal zoonosis, causing variant Creutzfeldt-Jakob disease in human beings. The ban on meat and bone meal in livestock feed and the removal of specified risk materials from the food chain were the main measures to successfully prevent infection in cattle and to protect human beings from BSE exposure. However, although BSE is now under control, previously unknown, so-called atypical transmissible spongiform encephalopathies (TSEs) in cattle and small ruminants have been identified by enhanced disease surveillance. This report briefly reviews and summarizes the current level of knowledge on the spectrum of TSEs in cattle and small ruminants and addresses the question of the extent to which such atypical TSEs have an effect on disease surveillance and control strategies. PMID:21088166

  13. Highly sensitive detection of small ruminant bovine spongiform encephalopathy within transmissible spongiform encephalopathy mixes by serial protein misfolding cyclic amplification.

    PubMed

    Gough, Kevin C; Bishop, Keith; Maddison, Ben C

    2014-11-01

    It is assumed that sheep and goats consumed the same bovine spongiform encephalopathy (BSE)-contaminated meat and bone meal that was fed to cattle and precipitated the BSE epidemic in the United Kingdom that peaked more than 20 years ago. Despite intensive surveillance for cases of BSE within the small ruminant populations of the United Kingdom and European Union, no instances of BSE have been detected in sheep, and in only two instances has BSE been discovered in goats. If BSE is present within the small ruminant populations, it may be at subclinical levels, may manifest as scrapie, or may be masked by coinfection with scrapie. To determine whether BSE is potentially circulating at low levels within the European small ruminant populations, highly sensitive assays that can specifically detect BSE, even within the presence of scrapie prion protein, are required. Here, we present a novel assay based on the specific amplification of BSE PrP(Sc) using the serial protein misfolding cyclic amplification assay (sPMCA), which specifically amplified small amounts of ovine and caprine BSE agent which had been mixed into a range of scrapie-positive brain homogenates. We detected the BSE prion protein within a large excess of classical, atypical, and CH1641 scrapie isolates. In a blind trial, this sPMCA-based assay specifically amplified BSE PrP(Sc) within brain mixes with 100% specificity and 97% sensitivity when BSE agent was diluted into scrapie-infected brain homogenates at 1% (vol/vol). PMID:25143565

  14. [Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies. Part I].

    PubMed

    Zaborowski, Adam

    2004-01-01

    In the first part of this work the main problems of prion diseases--also called transmissible cerebral amyloidoses (TCA) or subacute (transmissible) encephalopathies (SSE, TSE)--and clinical symptoms of Creutzfeldt-Jakob disease are presented. Some problems of neuropathology of Creutzfeldt-Jakob disease and basic informations about other human prion diseases will be presented in the second part. The growth of the interest in prion diseases during last years is caused by the problem of bovine spongiform encephalopathy (BSE or "mad cow disease") and its transmission into a human. The new variant of Creutzfeldt-Jakob disease (nvCJD) has appeared. Prion diseases: Gerstmann-Sträussler-Scheinker syndrome (GSS), kuru, fatal familial insomnia (FFI) and particularly the most frequent of them--Creutzfeldt-Jakob disease (CJD)--have nonspecific, sometimes variable clinical (psychopathological and neurological) symptoms. The imaging, EEG, cerebrospinal fluid tests and other laboratory tests are not specific either and their diagnostic value is limited. Neuropathological studies are needed but their interpretation is often difficult. The only certain diagnostic marker for TSE is the presence of PrP(Sc), the prion protein, which is presently believed to be a direct cause for all transmissible cerebral amyloidoses (TCA). PMID:15307293

  15. Analysis of risk to biomedical products developed from animal sources (with special emphasis on the spongiform encephalopathy agents, scrapie and BSE).

    PubMed

    Rohwer, R G

    1996-01-01

    Factors that must be considered in estimations of risk from exposure to adventitious contaminants of animal derived biologicals include: (i) the use of the product; (ii) the routes of administration and exposure to potential pathogens; (iii) the source of animal(s) and their history and maintenance; (iv) the tissue(s) used in the product and their likelihood of harbouring or being contaminated by an agent; (v) the methods by which the animal is slaughtered and the tissue(s) collected; (vi) the production process including steps that remove an agent either by inactivation or physical separation; (vii) the disposal of an agent that is sequestered but not inactivated; (viii) flow control, barriers, and between-batch cleaning; (ix) batch size; and (x) validations and quality assurance monitoring. The transmissible spongiform encephalopathy (TSE) agents, scrapie and bovine spongiform encephalopathy (BSE) are among the most difficult to detect and remove from animal tissues. As such they constitute an especially stringent challenge for viral clearance. PMID:9119146

  16. Dynamics of the natural transmission of bovine spongiform encephalopathy within an intensively managed sheep flock.

    PubMed

    Jeffrey, Martin; Witz, Janey P; Martin, Stuart; Hawkins, Steve A C; Bellworthy, Sue J; Dexter, Glenda E; Thurston, Lisa; González, Lorenzo

    2015-01-01

    Sheep are susceptible to the bovine spongiform encephalopathy (BSE) agent and in the UK they may have been exposed to BSE via contaminated meat and bone meal. An experimental sheep flock was established to determine whether ovine BSE could be naturally transmitted under conditions of intensive husbandry. The flock consisted of 113 sheep of different breeds and susceptible PRNP genotypes orally dosed with BSE, 159 sheep subsequently born to them and 125 unchallenged sentinel controls. BSE was confirmed in 104 (92%) orally dosed sheep and natural transmission was recorded for 14 of 79 (18%) lambs born to BSE infected dams, with rates varying according to PRNP genotype. The likelihood of natural BSE transmission was linked to stage of incubation period of the dam: the attack rate for lambs born within 100 days of the death of BSE infected dams was significantly higher (9/22, 41%) than for the rest (5/57, 9%). Within the group of ewes lambing close to death, those rearing infected progeny (n = 8, for 9/12 infected lambs) showed a significantly greater involvement of lymphoid tissues than those rearing non-infected offspring (n = 8, for 0/10 infected lambs). Horizontal transmission to the progeny of non-infected mothers was recorded only once (1/205, 0.5%). This low rate of lateral transmission was attributed, at least partly, to an almost complete absence of infected placentas. We conclude that, although BSE can be naturally transmitted through dam-lamb close contact, the infection in this study flock would not have persisted due to low-efficiency maternal and lateral transmissions. PMID:26511838

  17. Slow virus disease: deciphering conflicting data on the transmissible spongiform encephalopathies (TSE) also called prion diseases.

    PubMed

    Bastian, Frank O; Fermin, Cesar D

    2005-11-01

    The transmissible spongiform encephalopathies (TSE) that manifest as Creutzfeldt-Jakob disease in humans, as scrapie in sheep and goats, mad cow disease in cattle, or chronic wasting disease in cervids (deer) represent a serious human health crisis and a significant economical problem. Despite much research, the nature of the elusive pathogen directly involved with TSE is currently unresolved. This article reviews current pathogen-cell plasma membrane properties, showing that the primary biochemical marker of the prion disease is used as a receptor by the intracellular bacterium Brucella abortus. Such observation makes plausible the role for the prion in the pathogenesis of TSE, and supports the concept that Spiroplasma, a wall-less bacterium, may be a transmissible agent of TSE. Over the past three decades, we have published convincing evidence that Spiroplasma infection is associated with TSE. The bacterial-prion-receptor concept by other laboratories support a model for TSE wherein a Spiroplasma bacterium can bind to prion receptors (alone or with anchors) on the cell surface lipid raft, allowing entry of the microbe into the cell to initiate infection. The relevance of this new concept is that it offers a new window for future research involving a bacterium in the pathogenesis of TSE. Data from the bacterial-prion-receptor model will aid in the development diagnostic tests and/or treatment protocols for TSE. PMID:16276518

  18. Identification of a prion protein epitope modulating transmission of bovine spongiform encephalopathy prions to transgenic mice

    PubMed Central

    Scott, Michael R.; Safar, Jiri; Telling, Glenn; Nguyen, Oanh; Groth, Darlene; Torchia, Marilyn; Koehler, Ruth; Tremblay, Patrick; Walther, Dirk; Cohen, Fred E.; DeArmond, Stephen J.; Prusiner, Stanley B.

    1997-01-01

    There is considerable concern that bovine prions from cattle with bovine spongiform encephalopathy (BSE) may have been passed to humans (Hu), resulting in a new form of Creutzfeldt–Jakob disease (CJD). We report here the transmission of bovine (Bo) prions to transgenic (Tg) mice expressing BoPrP; one Tg line exhibited incubation times of ≈200 days. Like most cattle with BSE, vacuolation and astrocytic gliosis were confined in the brainstems of these Tg mice. Unexpectedly, mice expressing a chimeric Bo/Mo PrP transgene were resistant to BSE prions whereas mice expressing Hu or Hu/Mo PrP transgenes were susceptible to Hu prions. A comparison of differences in Mo, Bo, and Hu residues within the C terminus of PrP defines an epitope that modulates conversion of PrPC into PrPSc and, as such, controls prion transmission across species. Development of susceptible Tg(BoPrP) mice provides a means of measuring bovine prions that may prove critical in minimizing future human exposure. PMID:9405603

  19. Mechanism of PrP-amyloid formation in mice without transmissible spongiform encephalopathy

    PubMed Central

    Jeffrey, Martin; McGovern, Gillian; Chambers, Emily V.; King, Declan; González, Lorenzo; Manson, Jean C.; Ghetti, Bernardino; Piccardo, Pedro; Barron, Rona M.

    2011-01-01

    Gerstmann-Sträussler-Scheinker (GSS) P102L disease is a familial form of a transmissible spongiform encephalopathy (TSE) that can present with or without vacuolation of neuropil. Inefficient disease transmission into 101LL transgenic mice was previously observed from GSS P102L without vacuolation. However several aged, healthy mice had large plaques composed of abnormal prion protein (PrPd). Here we perform the ultrastructural characterisation of such plaques and compare them with PrPd aggregates found in TSE caused by an infectious mechanism. PrPd plaques in 101LL mice varied in maturity with some being composed of deposits without visible amyloid fibrils. PrPd was present on cell membranes in the vicinity of all types of plaques. In contrast to the unicentric plaques seen in infectious murine scrapie the plaques seen in the current model were multi-centric and were initiated by proto-fibrillar forms of PrPd situated on oligodendroglia, astrocytes and neuritic cell membranes. We speculate that the initial conversion process leading to plaque formation begins with membrane-bound PrPC but that subsequent fibrillisation does not require membrane attachment. We also observed that the membrane alterations consistently seen in murine scrapie and other infectious TSEs were not observed in 101LL mice with plaques suggesting differences in the pathogenesis of these conditions. PMID:21645162

  20. Experimental transmission of transmissible spongiform encephalopathies (scrapie, chronic wasting disease, transmissible mink encephalopathy) to cattle and their differentiation from bovine spongiform encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Experimental cross-species transmission of TSE agents provides valuable information for identification of potential host ranges of known TSEs. This report provides a synopsis of TSE (scrapie, CWD, TME) transmission studies that have been conducted in cattle and compares these findings to...

  1. Experimental transmission of transmissible spongiform encephalopathies (scrapie, chronic wasting disease, transmissible mink encephalopathy) to cattle and their differentiation from bovine spongiform encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Experimental cross-species transmission of TSE agents provides valuable information for identification of potential host ranges of known TSEs. This report provides a synopsis of TSE (scrapie, CWD, TME) transmission studies that have been conducted in cattle and compares these findings...

  2. Experimental transmission of transmissible spongiform encephalopathies (scrapie, chronic wasting disease, transmissible mink encephalopathy) to cattle and their differentiation from bovine spongiform encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Experimental cross-species transmission of TSE agents provides valuable information for identification of potential host ranges of known TSEs. This report provides a synopsis of TSE (scrapie, CWD, TME) transmission studies that have been conducted in cattle and compares these findings to those seen ...

  3. Post-translational changes to PrP alter transmissible spongiform encephalopathy strain properties

    PubMed Central

    Cancellotti, Enrico; Mahal, Sukhvir P; Somerville, Robert; Diack, Abigail; Brown, Deborah; Piccardo, Pedro; Weissmann, Charles; Manson, Jean C

    2013-01-01

    The agents responsible for transmissible spongiform encephalopathies (TSEs), or prion diseases, contain as a major component PrPSc, an abnormal conformer of the host glycoprotein PrPC. TSE agents are distinguished by differences in phenotypic properties in the host, which nevertheless can contain PrPSc with the same amino-acid sequence. If PrP alone carries information defining strain properties, these must be encoded by post-translational events. Here we investigated whether the glycosylation status of host PrP affects TSE strain characteristics. We inoculated wild-type mice with three TSE strains passaged through transgenic mice with PrP devoid of glycans at the first, second or both N-glycosylation sites. We compared the infectious properties of the emerging isolates with TSE strains passaged in wild-type mice by in vivo strain typing and by the standard scrapie cell assay in vitro. Strain-specific characteristics of the 79A TSE strain changed when PrPSc was devoid of one or both glycans. Thus infectious properties of a TSE strain can be altered by post-translational changes to PrP which we propose result in the selection of mutant TSE strains. PMID:23395905

  4. Comparative studies on the thermostability of five strains of transmissible-spongiform-encephalopathy agent.

    PubMed

    Fernie, Karen; Steele, Philip J; Taylor, David M; Somerville, Robert A

    2007-08-01

    The causal infectious agents of TSEs (transmissible spongiform encephalopathies or prion diseases) are renowned for their resistance to complete inactivation. Survival of TSE infectivity after autoclaving potentially compromises many procedures where TSE infectivity may be present, including surgical instrument sterilization. In the present study, the heat inactivation properties of five different TSE agents were tested in a variety of experiments by exposing them to a range of heat inactivation conditions. Although TSE infectivity was reduced after heating to 200 degrees C in a hot air oven, substantial amounts of infectivity remained. Unlike wet heat inactivation, no TSE strain-dependent differences were observed in the reduction in the amounts of infectivity produced by dry heat inactivation. However, the incubation periods of mice infected with one dry heated TSE strain, ME7, were substantially prolonged, whereas there was little or no effect for two other TSE models. Varying autoclaving conditions for three TSE strains between 132 and 138 degrees C, and times of exposure between 30 and 120 min, had little or no effect on the recovery of TSE infectivity. The results illustrate the limitations of TSE agent inactivation using heat-based methods. The results support the hypothesis that the structures of TSE agents are stabilized during heat-inactivation procedures, rendering them much more refractory to inactivation. This may occur through dehydration of the causal agents, specifically through the removal of the water of solvation from agent structures and hence stabilize interactions between prion protein and TSE agent-specific ligands. PMID:17331068

  5. Spatial correlation between the prevalence of transmissible spongiform diseases and British soil geochemistry.

    PubMed

    Imrie, C E; Korre, A; Munoz-Melendez, G

    2009-02-01

    Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurological conditions affecting a number of mammals, including sheep and goats (scrapie), cows (BSE), and humans (Creutzfeldt-Jakob disease). The diseases are widely believed to be caused by the misfolding of the normal prion protein to a pathological isoform, which is thought to act as an infectious agent. Outbreaks of the disease are commonly attributed to contaminated feed and genetic susceptibility. However, the implication of copper and manganese in the pathology of the disease, and its apparent geographical clustering, have prompted suggestions of a link with trace elements in the environment. Nevertheless, studies of soils at regional scales have failed to provide evidence of an environmental risk factor. This study uses geostatistical techniques to investigate the correlations between the distribution of TSE prevalence and soil geochemical variables across the UK according to different spatial scales. A similar spatial pattern in scrapie and BSE occurrence is identified, which may be linked with increasing pH and total organic carbon, and decreasing iodine concentration. However, the pattern also resembles that of the density of dairy farming. Nevertheless, despite the low spatial resolution of the TSE data available for this study, the fact that significant correlations are detected indicates there is a possibility of a link between soil geochemistry, scrapie, and BSE. It is suggested that further investigations of the prevalence of TSE and environmental exposure to trace metals should take into account the factors affecting their bioavailability. PMID:18427934

  6. Transmissibility of H-Type Bovine Spongiform Encephalopathy to Hamster PrP Transgenic Mice

    PubMed Central

    Okada, Hiroyuki; Masujin, Kentaro; Miyazawa, Kohtaro; Yokoyama, Takashi

    2015-01-01

    Two distinct forms of atypical bovine spongiform encephalopathies (H-BSE and L-BSE) can be distinguished from classical (C-) BSE found in cattle based on biochemical signatures of disease-associated prion protein (PrPSc). H-BSE is transmissible to wild-type mice—with infected mice showing a long survival period that is close to their normal lifespan—but not to hamsters. Therefore, rodent-adapted H-BSE with a short survival period would be useful for analyzing H-BSE characteristics. In this study, we investigated the transmissibility of H-BSE to hamster prion protein transgenic (TgHaNSE) mice with long survival periods. Although none of the TgHaNSE mice manifested the disease during their lifespan, PrPSc accumulation was observed in some areas of the brain after the first passage. With subsequent passages, TgHaNSE mice developed the disease with a mean survival period of 220 days. The molecular characteristics of proteinase K-resistant PrPSc (PrPres) in the brain were identical to those observed in first-passage mice. The distribution of immunolabeled PrPSc in the brains of TgHaNSE mice differed between those infected with H-BSE as compared to C-BSE or L-BSE, and the molecular properties of PrPres in TgHaNSE mice infected with H-BSE differed from those of the original isolate. The strain-specific electromobility, glycoform profiles, and proteolytic cleavage sites of H-BSE in TgHaNSE mice were indistinguishable from those of C-BSE, in which the diglycosylated form was predominant. These findings indicate that strain-specific pathogenic characteristics and molecular features of PrPres in the brain are altered during cross-species transmission. Typical H-BSE features were restored after back passage from TgHaNSE to bovinized transgenic mice, indicating that the H-BSE strain was propagated in TgHaNSE mice. This could result from the overexpression of the hamster prion protein. PMID:26466381

  7. Surveillance for Transmissible Spongiform Encephalopathy in Scavengers of White-Tailed Deer Carcasses in the Chronic Wasting Disease Area of Wisconsin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic wasting disease (CWD), a class of neurodegenerative transmissible spongiform encephalopathies (TSE) occurring in cervids, is found in a number of states and provinces across North America. Misfolded prions, the infectious agents of CWD, are deposited in the environment via carcass remains an...

  8. Trends in scientific activity addressing transmissible spongiform encephalopathies: a bibliometric study covering the period 1973–2002

    PubMed Central

    Sanz-Casado, Elías; Ramírez-de Santa Pau, Margarita; Suárez-Balseiro, Carlos A; Iribarren-Maestro, Isabel; de Pedro-Cuesta, Jesús

    2006-01-01

    Background The purpose of this study is to analyse the trends in scientific research on transmissible spongiform encephalopathies by applying bibliometric tools to the scientific literature published between 1973 and 2002. Methods The data for the study were obtained from Medline database, in order to determine the volume of scientific output in the above period, the countries involved, the type of document and the trends in the subject matters addressed. The period 1973–2002 was divided in three sub-periods. Results We observed a significant growth in scientific production. The percentage of increase is 871.7 from 1973 to 2002. This is more evident since 1991 and particularly in the 1996–2001 period. The countries found to have the highest output were the United States, the United Kingdom, Japan, France and Germany. The evolution in the subject matters was almost constant in the three sub-periods in which the study was divided. In the first and second sub-periods, the subject matters of greatest interest were more general, i.e Nervous system or Nervous system diseases, Creutzfeldt-Jakob disease, Scrapie, and Chemicals and Drugs, but in the last sub-period, some changes were observed because the Prion-related matters had the greatest presence. Collaboration among authors is small from 1973 to 1992, but increases notably in the third sub-period, and also the number of authors and clusters formed. Some of the authors, like Gajdusek or Prusiner, appear in the whole period. Conclusion The study reveals a very high increase in scientific production. It is related also with the beginnings of research on bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease, with the establishment of progressive collaboration relationships and a reflection of public health concerns about this problem. PMID:17026743

  9. Elimination of transmissible spongiform encephalopathy infectivity and decontamination of surgical instruments by using radio-frequency gas-plasma treatment.

    PubMed

    Baxter, H C; Campbell, G A; Whittaker, A G; Jones, A C; Aitken, A; Simpson, A H; Casey, M; Bountiff, L; Gibbard, L; Baxter, R L

    2005-08-01

    It has now been established that transmissible spongiform encephalopathy (TSE) infectivity, which is highly resistant to conventional methods of deactivation, can be transmitted iatrogenically by contaminated stainless steel. It is important that new methods are evaluated for effective removal of protein residues from surgical instruments. Here, radio-frequency (RF) gas-plasma treatment was investigated as a method of removing both the protein debris and TSE infectivity. Stainless-steel spheres contaminated with the 263K strain of scrapie and a variety of used surgical instruments, which had been cleaned by a hospital sterile-services department, were examined both before and after treatment by RF gas plasma, using scanning electron microscopy and energy-dispersive X-ray spectroscopic analysis. Transmission of scrapie from the contaminated spheres was examined in hamsters by the peripheral route of infection. RF gas-plasma treatment effectively removed residual organic residues on reprocessed surgical instruments and gross contamination both from orthopaedic blades and from the experimentally contaminated spheres. In vivo testing showed that RF gas-plasma treatment of scrapie-infected spheres eliminated transmission of infectivity. The infectivity of the TSE agent adsorbed on metal spheres could be removed effectively by gas-plasma cleaning with argon/oxygen mixtures. This treatment can effectively remove 'stubborn' residual contamination on surgical instruments. PMID:16033987

  10. Acquired transmissibility of sheep-passaged L-type bovine spongiform encephalopathy prion to wild-type mice.

    PubMed

    Okada, Hiroyuki; Masujin, Kentaro; Miyazawa, Kohtaro; Yokoyama, Takashi

    2015-01-01

    L-type bovine spongiform encephalopathy (L-BSE) is an atypical form of BSE that is transmissible to cattle and several lines of prion protein (PrP) transgenic mice, but not to wild-type mice. In this study, we examined the transmissibility of sheep-passaged L-BSE prions to wild-type mice. Disease-associated prion protein (PrP(Sc)) was detected in the brain and/or lymphoid tissues during the lifespan of mice that were asymptomatic subclinical carriers, indicating that wild-type mice were susceptible to sheep-passaged L-BSE. The morphological characteristics of the PrP(Sc) of sheep-passaged L-BSE included florid plaques that were distributed mainly in the cerebral cortex and hippocampus of subsequent passaged mice. The PrP(Sc) glycoform profiles of wild-type mice infected with sheep-passaged L-BSE were similar to those of the original isolate. The data indicate that sheep-passaged L-BSE has an altered host range and acquired transmissibility to wild-type mice. PMID:26169916

  11. Human and animal spongiform encephalopathies are the result of chronic autoimmune attack in the CNS: a novel medical theory supported by overwhelming experimental evidence.

    PubMed

    Zhu, B T

    2005-04-01

    Spongiform encephalopathies, also called "prion diseases", are fatal degenerative diseases of the central nervous system which can occur in animals (such as the "mad cow disease" in cattle) and also in humans. This paper presents a novel medical theory concerning the pathogenic mechanisms for various human and animal spongiform encephalopathies. It is hypothesized that various forms of prion diseases are essentially autoimmune diseases, resulting from chronic autoimmune attack of the central nervous system. A key step in the pathogenic process leading towards the development of spongiform encephalopathies involves the production of specific autoimmune antibodies against the disease-causing prion protein (PrPsc) and possibly other immunogenic macromolecules present in the brain. As precisely explained in this paper, the autoimmune antibodies produced against PrPsc are responsible for the conversion of the normal cellular prion protein (PrPc) to PrPsc, for the accumulation of PrPsc in the brain and other peripheral tissues, and also for the initiation of an antibody-mediated chronic autoimmune attack of the central nervous system neurons, which would contribute to the development of characteristic pathological changes and clinical symptoms associated with spongiform encephalopathies. The validity and correctness of the proposed theory is supported by an overwhelming body of experimental observations that are scattered in the biomedical literature. In addition, the theory also offers practical new strategies for early diagnosis, treatment, and prevention of various human and animal prion diseases. PMID:15736062

  12. Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein.

    PubMed

    Wilson, Rona; Plinston, Chris; Hunter, Nora; Casalone, Cristina; Corona, Cristiano; Tagliavini, Fabrizio; Suardi, Silvia; Ruggerone, Margherita; Moda, Fabio; Graziano, Silvia; Sbriccoli, Marco; Cardone, Franco; Pocchiari, Maurizio; Ingrosso, Loredana; Baron, Thierry; Richt, Juergen; Andreoletti, Olivier; Simmons, Marion; Lockey, Richard; Manson, Jean C; Barron, Rona M

    2012-07-01

    The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. In recent years, several novel TSEs in sheep, cattle and deer have been described and the risk posed to humans by these agents is currently unknown. In this study, we inoculated two forms of atypical BSE (BASE and H-type BSE), a chronic wasting disease (CWD) isolate and seven isolates of atypical scrapie into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP). Upon challenge with these ruminant TSEs, gene-targeted Tg mice expressing human PrP did not show any signs of disease pathology. These data strongly suggest the presence of a substantial transmission barrier between these recently identified ruminant TSEs and humans. PMID:22495232

  13. Animal Meal: Production and Determination in Feedstuffs and the Origin of Bovine Spongiform Encephalopathy

    NASA Astrophysics Data System (ADS)

    Hahn, Heinz

    This contribution examines what animal meal is, how it is produced in rendering plants, and means of investigating feedstuff constituents. In addition to animal meal, numerous other products of animal origin are also on the market (e.g., blood meal, bone meal, feather meal, gelatin). Constituents of animal origin can be detected in feedstuffs by microscopy, but determining the animal species from which the constituents are derived, as required by law in Germany, requires methods such as enzyme-linked immunosorbent assay and polymerase chain reaction. We consider the problem of trace contamination being introduced accidentally during the production of ruminants' feedstuffs containing constituents of animal origin. The future of animal meal is discussed together with alternatives for disposing of animal carcasses and slaughtery offal, i.e., composting and incineration.

  14. Abnormalities in Brainstem Auditory Evoked Potentials in Sheep with Transmissible Spongiform Encephalopathies and Lack of a Clear Pathological Relationship.

    PubMed

    Konold, Timm; Phelan, Laura J; Cawthraw, Saira; Simmons, Marion M; Chaplin, Melanie J; González, Lorenzo

    2016-01-01

    Scrapie is transmissible spongiform encephalopathy (TSE), which causes neurological signs in sheep, but confirmatory diagnosis is usually made postmortem on examination of the brain for TSE-associated markers like vacuolar changes and disease-associated prion protein (PrP(Sc)). The objective of this study was to evaluate whether testing of brainstem auditory evoked potentials (BAEPs) at two different sound levels could aid in the clinical diagnosis of TSEs in sheep naturally or experimentally infected with different TSE strains [classical and atypical scrapie and bovine spongiform encephalopathy (BSE)] and whether any BAEP abnormalities were associated with TSE-associated markers in the auditory pathways. BAEPs were recorded from 141 clinically healthy sheep of different breeds and ages that tested negative for TSEs on postmortem tests to establish a reference range and to allow comparison with 30 sheep clinically affected or exposed to classical scrapie (CS) without disease confirmation (test group 1) and 182 clinically affected sheep with disease confirmation (test group 2). Abnormal BAEPs were found in 7 sheep (23%) of group 1 and 42 sheep (23%) of group 2. The proportion of sheep with abnormalities did not appear to be influenced by TSE strain or PrP(Sc) gene polymorphisms. When the magnitude of TSE-associated markers in the auditory pathways was compared between a subset of 12 sheep with and 12 sheep without BAEP abnormalities in group 2, no significant differences in the total PrP(Sc) or vacuolation scores in the auditory pathways could be found. However, the data suggested that there was a difference in the PrP(Sc) scores depending on the TSE strain because PrP(Sc) scores were significantly higher in sheep with BAEP abnormalities infected with classical and L-type BSE, but not with CS. The results indicated that BAEPs may be abnormal in sheep infected with TSEs but the test is not specific for TSEs and that neither vacuolation nor PrP(Sc) accumulation

  15. Abnormalities in Brainstem Auditory Evoked Potentials in Sheep with Transmissible Spongiform Encephalopathies and Lack of a Clear Pathological Relationship

    PubMed Central

    Konold, Timm; Phelan, Laura J.; Cawthraw, Saira; Simmons, Marion M.; Chaplin, Melanie J.; González, Lorenzo

    2016-01-01

    Scrapie is transmissible spongiform encephalopathy (TSE), which causes neurological signs in sheep, but confirmatory diagnosis is usually made postmortem on examination of the brain for TSE-associated markers like vacuolar changes and disease-associated prion protein (PrPSc). The objective of this study was to evaluate whether testing of brainstem auditory evoked potentials (BAEPs) at two different sound levels could aid in the clinical diagnosis of TSEs in sheep naturally or experimentally infected with different TSE strains [classical and atypical scrapie and bovine spongiform encephalopathy (BSE)] and whether any BAEP abnormalities were associated with TSE-associated markers in the auditory pathways. BAEPs were recorded from 141 clinically healthy sheep of different breeds and ages that tested negative for TSEs on postmortem tests to establish a reference range and to allow comparison with 30 sheep clinically affected or exposed to classical scrapie (CS) without disease confirmation (test group 1) and 182 clinically affected sheep with disease confirmation (test group 2). Abnormal BAEPs were found in 7 sheep (23%) of group 1 and 42 sheep (23%) of group 2. The proportion of sheep with abnormalities did not appear to be influenced by TSE strain or PrPSc gene polymorphisms. When the magnitude of TSE-associated markers in the auditory pathways was compared between a subset of 12 sheep with and 12 sheep without BAEP abnormalities in group 2, no significant differences in the total PrPSc or vacuolation scores in the auditory pathways could be found. However, the data suggested that there was a difference in the PrPSc scores depending on the TSE strain because PrPSc scores were significantly higher in sheep with BAEP abnormalities infected with classical and L-type BSE, but not with CS. The results indicated that BAEPs may be abnormal in sheep infected with TSEs but the test is not specific for TSEs and that neither vacuolation nor PrPSc accumulation appears to be

  16. Prion biology relevant to bovine spongiform encephalopathy.

    PubMed

    Novakofski, J; Brewer, M S; Mateus-Pinilla, N; Killefer, J; McCusker, R H

    2005-06-01

    Bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) of deer and elk are a threat to agriculture and natural resources, as well as a human health concern. Both diseases are transmissible spongiform encephalopathies (TSE), or prion diseases, caused by autocatalytic conversion of endogenously encoded prion protein (PrP) to an abnormal, neurotoxic conformation designated PrPsc. Most mammalian species are susceptible to TSE, which, despite a range of species-linked names, is caused by a single highly conserved protein, with no apparent normal function. In the simplest sense, TSE transmission can occur because PrPsc is resistant to both endogenous and environmental proteinases, although many details remain unclear. Questions about the transmission of TSE are central to practical issues such as livestock testing, access to international livestock markets, and wildlife management strategies, as well as intangible issues such as consumer confidence in the safety of the meat supply. The majority of BSE cases seem to have been transmitted by feed containing meat and bone meal from infected animals. In the United Kingdom, there was a dramatic decrease in BSE cases after neural tissue and, later, all ruminant tissues were banned from ruminant feed. However, probably because of heightened awareness and widespread testing, there is growing evidence that new variants of BSE are arising "spontaneously," suggesting ongoing surveillance will continue to find infected animals. Interspecies transmission is inefficient and depends on exposure, sequence homology, TSE donor strain, genetic polymorphism of the host, and architecture of the visceral nerves if exposure is by an oral route. Considering the low probability of interspecies transmission, the low efficiency of oral transmission, and the low prion levels in nonnervous tissues, consumption of conventional animal products represents minimal risk. However, detection of rare events is challenging, and TSE

  17. Susceptibility of European red deer (Cervus elaphus elaphus) to alimentary challenge with bovine spongiform encephalopathy.

    PubMed

    Dagleish, Mark P; Martin, Stuart; Steele, Philip; Finlayson, Jeanie; Eaton, Samantha L; Sisó, Sílvia; Stewart, Paula; Fernández-Borges, Natalia; Hamilton, Scott; Pang, Yvonne; Chianini, Francesca; Reid, Hugh W; Goldmann, Wilfred; González, Lorenzo; Castilla, Joaquín; Jeffrey, Martin

    2015-01-01

    European red deer (Cervus elaphus elaphus) are susceptible to the agent of bovine spongiform encephalopathy, one of the transmissible spongiform encephalopathies, when challenged intracerebrally but their susceptibility to alimentary challenge, the presumed natural route of transmission, is unknown. To determine this, eighteen deer were challenged via stomach tube with a large dose of the bovine spongiform encephalopathy agent and clinical signs, gross and histological lesions, presence and distribution of abnormal prion protein and the attack rate recorded. Only a single animal developed clinical disease, and this was acute with both neurological and respiratory signs, at 1726 days post challenge although there was significant (27.6%) weight loss in the preceding 141 days. The clinically affected animal had histological lesions of vacuolation in the neuronal perikaryon and neuropil, typical of transmissible spongiform encephalopathies. Abnormal prion protein, the diagnostic marker of transmissible encephalopathies, was primarily restricted to the central and peripheral nervous systems although a very small amount was present in tingible body macrophages in the lymphoid patches of the caecum and colon. Serial protein misfolding cyclical amplification, an in vitro ultra-sensitive diagnostic technique, was positive for neurological tissue from the single clinically diseased deer. All other alimentary challenged deer failed to develop clinical disease and were negative for all other investigations. These findings show that transmission of bovine spongiform encephalopathy to European red deer via the alimentary route is possible but the transmission rate is low. Additionally, when deer carcases are subjected to the same regulations that ruminants in Europe with respect to the removal of specified offal from the human food chain, the zoonotic risk of bovine spongiform encephalopathy, the cause of variant Creutzfeldt-Jakob disease, from consumption of venison is probably

  18. Bovine Spongiform Encephalopathy: what is "Atypical BSE" and can we detect it?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transmissible spongiform encephalopathy (TSE) agents induce fatal neurodegenerative diseases in humans and in some other mammalian species. Human TSEs include Creutzfeldt–Jakob disease (CJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, Kuru and Fatal Familial Insomnia (FFI). In animals, several d...

  19. Food Safety: Bovine Spongiform Encephalopathy (Mad Cow Disease).

    PubMed

    Acheson, David W. K.

    2002-01-01

    Bovine spongiform encephalopathy is just one of a group of diseases known as transmissible spongiform encephalopathies. Only recently has it become recognized that transmissible spongiform encephalopathies are likely due to proteins known as prions. Although it has been recognized that transmissible spongiform encephalopathies may readily spread within species, the recent observations that bovine spongiform encephalopathy in cattle may have originated from another transmissible spongiform encephalopathy in sheep, known as scrapie, is cause for concern. Further, bovine spongiform encephalopathy has now been strongly linked with a universally fatal human neurologic disease known as new variant Creutzfeldt-Jakob disease. Currently the only approach to preventing bovine spongiform encephalopathy, and subsequent new variant Creutzfeldt-Jakob disease in humans, from ingestion of bovine spongiform encephalopathy-infected material is to avoid consumption of contaminated food. Little can be done to treat food that will destroy prions and leave a palatable product. At this stage we are continuing to learn about transmissible spongiform encephalopathies and their implications on human health. This is an ever-changing situation and has an unpredictable element in terms of the extent of the current outbreaks in England and other parts of Europe. PMID:11984426

  20. Surveillance for transmissible spongiform encephalopathy in scavengers of white-tailed deer carcasses in the chronic wasting disease area of wisconsin

    USGS Publications Warehouse

    Jennelle, C.S.; Samuel, M.D.; Nolden, C.A.; Keane, D.P.; Barr, D.J.; Johnson, Chad; Vanderloo, J.P.; Aiken, Judd M.; Hamir, A.N.; Hoover, E.A.

    2009-01-01

    Chronic wasting disease (CWD), a class of neurodegenerative transmissible spongiform encephalopathies (TSE) occurring in cervids, is found in a number of states and provinces across North America. Misfolded prions, the infectious agents of CWD, are deposited in the environment via carcass remains and excreta, and pose a threat of cross-species transmission. In this study tissues were tested from 812 representative mammalian scavengers, collected in the CWD-affected area of Wisconsin, for TSE infection using the IDEXX HerdChek enzyme-linked immunosorbent assay (ELISA). Only four of the collected mammals tested positive using the ELISA, but these were negative when tested by Western blot. While our sample sizes permitted high probabilities of detecting TSE assuming 1% population prevalence in several common scavengers (93%, 87%, and 87% for raccoons, opossums, and coyotes, respectively), insufficient sample sizes for other species precluded similar conclusions. One cannot rule out successful cross-species TSE transmission to scavengers, but the results suggest that such transmission is not frequent in the CWD-affected area of Wisconsin. The need for further surveillance of scavenger species, especially those known to be susceptible to TSE (e.g., cat, American mink, raccoon), is highlighted in both a field and laboratory setting.

  1. An overview of animal prion diseases

    PubMed Central

    2011-01-01

    Prion diseases are transmissible neurodegenerative conditions affecting human and a wide range of animal species. The pathogenesis of prion diseases is associated with the accumulation of aggregates of misfolded conformers of host-encoded cellular prion protein (PrPC). Animal prion diseases include scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, transmissible mink encephalopathy, feline spongiform encephalopathy, exotic ungulate spongiform encephalopathy, chronic wasting disease of cervids and spongiform encephalopathy of primates. Although some cases of sporadic atypical scrapie and BSE have also been reported, animal prion diseases have basically occurred via the acquisition of infection from contaminated feed or via the exposure to contaminated environment. Scrapie and chronic wasting disease are naturally sustaining epidemics. The transmission of BSE to human has caused more than 200 cases of variant Cruetzfeldt-Jacob disease and has raised serious public health concerns. The present review discusses the epidemiology, clinical neuropathology, transmissibility and genetics of animal prion diseases. PMID:22044871

  2. An overview of animal prion diseases.

    PubMed

    Imran, Muhammad; Mahmood, Saqib

    2011-01-01

    Prion diseases are transmissible neurodegenerative conditions affecting human and a wide range of animal species. The pathogenesis of prion diseases is associated with the accumulation of aggregates of misfolded conformers of host-encoded cellular prion protein (PrPC). Animal prion diseases include scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, transmissible mink encephalopathy, feline spongiform encephalopathy, exotic ungulate spongiform encephalopathy, chronic wasting disease of cervids and spongiform encephalopathy of primates. Although some cases of sporadic atypical scrapie and BSE have also been reported, animal prion diseases have basically occurred via the acquisition of infection from contaminated feed or via the exposure to contaminated environment. Scrapie and chronic wasting disease are naturally sustaining epidemics. The transmission of BSE to human has caused more than 200 cases of variant Cruetzfeldt-Jacob disease and has raised serious public health concerns. The present review discusses the epidemiology, clinical neuropathology, transmissibility and genetics of animal prion diseases. PMID:22044871

  3. Transmission of systemic AA amyloidosis in animals.

    PubMed

    Murakami, T; Ishiguro, N; Higuchi, K

    2014-03-01

    Amyloidoses are a group of protein-misfolding disorders that are characterized by the deposition of amyloid fibrils in organs and/or tissues. In reactive amyloid A (AA) amyloidosis, serum AA (SAA) protein forms deposits in mice, domestic and wild animals, and humans that experience chronic inflammation. AA amyloid fibrils are abnormal β-sheet-rich forms of the serum precursor SAA, with conformational changes that promote fibril formation. Extracellular deposition of amyloid fibrils causes disease in affected animals. Recent findings suggest that AA amyloidosis could be transmissible. Similar to the pathogenesis of transmissible prion diseases, amyloid fibrils induce a seeding-nucleation process that may lead to development of AA amyloidosis. We review studies of possible transmission in bovine, avian, mouse, and cheetah AA amyloidosis. PMID:24280941

  4. In-situ spectroscopic investigation of transmissible spongiform encephalopathies: application of Fourier-transform infrared spectroscopy to a scrapie-hamster model

    NASA Astrophysics Data System (ADS)

    Kneipp, Janina; Lasch, Peter; Beekes, Michael; Naumann, Dieter

    2002-03-01

    Transmissible spongiform encephalopathies (TSE), such as BSE in cattle, scrapie in sheep and goats, and Creutzfeldt-Jakob disease in man are a group of fatal infectious diseases of the central nervous system that are far from being fully understood. Presuming the pathological changes to originate from small disease-specific compositional and structural modifications at the molecular level, Fourier-transform infrared (FTIR) spectroscopy can be used to achieve insight into biochemical parameters underlying pathogenesis. We have developed an FTIR microspectroscopy-based strategy which, as a combination of image reconstruction and multivariate pattern recognition methods, permitted the comparison of identical substructures in the cerebellum of healthy and TSE-infected Syrian hamsters in the terminal stage of the disease. Here we present FTIR data about the pathological changes of scrapie-infected and normal tissue of the gray matter structures stratum granulosum and stratum moleculare. IR spectroscopy was also applied to tissue pieces of the medulla oblongata of infected and control Syrian hamsters. Mapping data were analyzed with cluster analysis and imaging methods. We found variations in the spectra of the infected tissue, which are due to changes in carbohydrates, nucleic acids, phospholipids, and proteins.

  5. Typical and atypical cases of bovine spongiform encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy of cattle, first detected in 1986 in the United Kingdom and subsequently in other countries. It is the most likely cause of variant Creutzfeldt-Jakob disease (vCJD) in humans, but the origin of BSE has not been eluci...

  6. 70 FR 18251 - Bovine Spongiform Encephalopathy; Minimal-Risk Regions and Importation of Commodities; Finding of...

    Code of Federal Regulations, 2014 CFR

    2005-04-08

    ... Agriculture Animal and Plant Health Inspection Service 9 CFR Part 93, et al. Bovine Spongiform Encephalopathy... Implementing Procedures (7 CFR part 372). Bovine Spongiform Encephalopathy; Minimal-Risk Regions and... pointed to the four confirmed cases of bovine spongiform encephalopathy (BSE) in cows of Canadian...

  7. Quantitative Risk Assessment of Bovine Spongiform Encephalopathy

    NASA Astrophysics Data System (ADS)

    Tsutsui, Toshiyuki; Kasuga, Fumiko

    Bovine spongiform encephalopathy (BSE) is a progressive neurological disease of cattle affecting the central nervous system and was first diagnosed in the United Kingdom (UK) in 1986 (Wells et al., 1987). This disease is one of the transmissible spongiform encephalopathy (TSE) which includes Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep. The causative agent of TSE is considered to be an abnormal form of prion protein. However, the details of its pathogenic mechanism have not been fully identified. Scrapie, which causes neurological symptoms in sheep and goats, has existed in the UK for 200 years (Hoinville, 1996) and spread across the rest of the world in the 1900s (Detwiler & Baylis, 2003). There has been no report so far that scrapie can be transmitted to humans. Initially, BSE was also considered as a disease affecting only animals. However, a variant type of Creutzfeldt-Jakob disease (vCJD) was first reported in the UK, and exposure to a BSE agent was suspected (Collinge, Sidle, Meads, Ironside, & Hill, 1996). vCJD is clinically and pathologically different from the sporadic type of CJD, and age at clinical onset of vCJD is younger than sporadic type (Will et al., 1996). Since the UK government announced the possible association between BSE and vCJD in 1996, BSE has become a huge public health concern all over the world. Of particular concern about vCJD, the fatal disease in younger age, distorted consumer confidence in beef safety, and as a result reduced beef consumption has been seen in many BSE-affected countries.

  8. Removal of Transmissible Spongiform Encephalopathy Prion from Large Volumes of Cell Culture Media Supplemented with Fetal Bovine Serum by Using Hollow Fiber Anion-Exchange Membrane Chromatography

    PubMed Central

    Chou, Ming Li; Bailey, Andy; Avory, Tiffany; Tanimoto, Junji; Burnouf, Thierry

    2015-01-01

    Cases of variant Creutzfeldt-Jakob disease in people who had consumed contaminated meat products from cattle with bovine spongiform encephalopathy emphasize the need for measures aimed at preventing the transmission of the pathogenic prion protein (PrPSc) from materials derived from cattle. Highly stringent scrutiny is required for fetal bovine serum (FBS), a growth-medium supplement used in the production of parenteral vaccines and therapeutic recombinant proteins and in the ex vivo expansion of stem cells for transplantation. One such approach is the implementation of manufacturing steps dedicated to removing PrPSc from materials containing FBS. We evaluated the use of the QyuSpeed D (QSD) adsorbent hollow-fiber anion-exchange chromatographic column (Asahi Kasei Medical, Tokyo, Japan) for the removal of PrPSc from cell culture media supplemented with FBS. We first established that QSD filtration had no adverse effect on the chemical composition of various types of culture media supplemented with 10% FBS or the growth and viability characteristics of human embryonic kidney (HEK293) cells, baby hamster kidney (BHK-21) cells, African green monkey kidney (Vero) cells, and Chinese hamster ovary (CHO-k1) cells propagated in the various culture-medium filtrates. We used a 0.6-mL QSD column for removing PrPSc from up to 1000 mL of Dulbecco’s modified Eagle’s medium containing 10% FBS previously spiked with the 263K strain of hamster-adapted scrapie. The Western blot analysis, validated alongside an infectivity assay, revealed that the level of PrPSc in the initial 200mL flow-through was reduced by 2.5 to > 3 log10, compared with that of the starting material. These results indicate that QSD filtration removes PrPSc from cell culture media containing 10% FBS, and demonstrate the ease with which QSD filtration can be implemented in at industrial-scale to improve the safety of vaccines, therapeutic recombinant proteins, and ex vivo expanded stem cells produced using

  9. Transmissible Spongiform Encephalopathies (Prion Diseases)

    MedlinePlus

    ... when brain tissue is viewed under a microscope. Creutzfeldt-Jakob disease (CJD) is the most well-known of the ... and Worldwide NINDS Clinical Trials Organizations Column1 Column2 Creutzfeldt-Jakob Disease (CJD) Foundation Inc. 341 W. 38th Street, Suite ...

  10. [Bovine spongiform encephalopathy].

    PubMed

    Suárez Fernández, G

    2001-01-01

    An histórical and conceptual review is made about Bovine Spongiform Encephalopathy or mad cows disease and an epidemiological analysis as a present and future health problem. This analysis of BSE should not be negative, considering the truths that we know today. PMID:11783042

  11. Biochemical and immunohistochemical characterization of feline spongiform encephalopathy in a German captive cheetah.

    PubMed

    Eiden, Martin; Hoffmann, Christine; Balkema-Buschmann, Anne; Müller, Matthias; Baumgartner, Katrin; Groschup, Martin H

    2010-11-01

    Feline spongiform encephalopathy (FSE) is a transmissible spongiform encephalopathy that affects domestic cats (Felis catus) and captive wild members of the family Felidae. In this report we describe a case of FSE in a captive cheetah from the zoological garden of Nuremberg. The biochemical examination revealed a BSE-like pattern. Disease-associated scrapie prion protein (PrP(Sc)) was widely distributed in the central and peripheral nervous system, as well as in the lymphoreticular system and in other tissues of the affected animal, as demonstrated by immunohistochemistry and/or immunoblotting. Moreover, we report for the first time the use of the protein misfolding cyclic amplification technique for highly sensitive detection of PrP(Sc) in the family Felidae. The widespread PrP(Sc) deposition suggests a simultaneous lymphatic and neural spread of the FSE agent. The detection of PrP(Sc) in the spleen indicates a potential for prion infectivity of cheetah blood. PMID:20660146

  12. ANIMAL RESERVOIRS, VECTORS, AND TRANSMISSION OF MICROSPORIDIA

    EPA Science Inventory

    Fourteen species of microsporidia have been identified as opportunistic or emerging pathogens of humans. Several genotypes of Enterocytozoon bieneusi, the most frequently diagnosed species in humans, have been identified in Europe in farm and companion animals including pigs, cat...

  13. Expression transmission using exaggerated animation for Elfoid.

    PubMed

    Hori, Maiya; Tsuruda, Yu; Yoshimura, Hiroki; Iwai, Yoshio

    2015-01-01

    We propose an expression transmission system using a cellular-phone-type teleoperated robot called Elfoid. Elfoid has a soft exterior that provides the look and feel of human skin, and is designed to transmit the speaker's presence to their communication partner using a camera and microphone. To transmit the speaker's presence, Elfoid sends not only the voice of the speaker but also the facial expression captured by the camera. In this research, facial expressions are recognized using a machine learning technique. Elfoid cannot, however, display facial expressions because of its compactness and a lack of sufficiently small actuator motors. To overcome this problem, facial expressions are displayed using Elfoid's head-mounted mobile projector. In an experiment, we built a prototype system and experimentally evaluated it's subjective usability. PMID:26347686

  14. Expression transmission using exaggerated animation for Elfoid

    PubMed Central

    Hori, Maiya; Tsuruda, Yu; Yoshimura, Hiroki; Iwai, Yoshio

    2015-01-01

    We propose an expression transmission system using a cellular-phone-type teleoperated robot called Elfoid. Elfoid has a soft exterior that provides the look and feel of human skin, and is designed to transmit the speaker's presence to their communication partner using a camera and microphone. To transmit the speaker's presence, Elfoid sends not only the voice of the speaker but also the facial expression captured by the camera. In this research, facial expressions are recognized using a machine learning technique. Elfoid cannot, however, display facial expressions because of its compactness and a lack of sufficiently small actuator motors. To overcome this problem, facial expressions are displayed using Elfoid's head-mounted mobile projector. In an experiment, we built a prototype system and experimentally evaluated it's subjective usability. PMID:26347686

  15. Infectious disease in animal metapopulations: the importance of environmental transmission.

    PubMed

    Park, Andrew W

    2012-07-01

    Motivated by an array of infectious diseases that threaten wildlife populations, a simple metapopulation model (subpopulations connected by animal movement) is developed, which allows for both movement-based and environmental transmission. The model demonstrates that for a range of plausible parameterizations of environmental transmission, increased movement rate of animals between discrete habitats can lead to a decrease in the overall proportion of sites that are occupied. This can limit the ability of the rescue effect to ensure locally extinct populations become recolonized and can drive metapopulations down in size so that extinction by mechanisms other than disease may become more likely. It further highlights that, in the context of environmental transmission, the environmental persistence time of pathogens and the probability of acquiring infection by environmental transmission can affect host metapopulations both qualitatively and quantitatively. Additional spillover sources of infection from alternate reservoir hosts are also included in the model and a synthesis of all three types of transmission, acting alone or in combination, is performed revealing that movement-based transmission is the only necessary condition for a decline in the proportion of occupied sites with increasing movement rate, but that the presence of other types of transmission can reverse this qualitative result. By including the previously neglected role of environmental transmission, this work contributes to the general discussion of when dispersal by wild animals is beneficial or detrimental to populations experiencing infectious disease. PMID:22957148

  16. Infectious disease in animal metapopulations: the importance of environmental transmission

    PubMed Central

    Park, Andrew W

    2012-01-01

    Motivated by an array of infectious diseases that threaten wildlife populations, a simple metapopulation model (subpopulations connected by animal movement) is developed, which allows for both movement-based and environmental transmission. The model demonstrates that for a range of plausible parameterizations of environmental transmission, increased movement rate of animals between discrete habitats can lead to a decrease in the overall proportion of sites that are occupied. This can limit the ability of the rescue effect to ensure locally extinct populations become recolonized and can drive metapopulations down in size so that extinction by mechanisms other than disease may become more likely. It further highlights that, in the context of environmental transmission, the environmental persistence time of pathogens and the probability of acquiring infection by environmental transmission can affect host metapopulations both qualitatively and quantitatively. Additional spillover sources of infection from alternate reservoir hosts are also included in the model and a synthesis of all three types of transmission, acting alone or in combination, is performed revealing that movement-based transmission is the only necessary condition for a decline in the proportion of occupied sites with increasing movement rate, but that the presence of other types of transmission can reverse this qualitative result. By including the previously neglected role of environmental transmission, this work contributes to the general discussion of when dispersal by wild animals is beneficial or detrimental to populations experiencing infectious disease. PMID:22957148

  17. A collaborative Canadian-United Kingdom evaluation of an immunohistochemistry protocol to diagnose bovine spongiform encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy is a transmissible spongiform encephalopathy of domestic cattle. The disorder was reported in the United Kingdom in the late 1980s and was associated with recycling of ruminant byproducts in cattle feed. In 1996, the bovine disease was reported to be the cause of a...

  18. Autoantibodies to Brain Components and Antibodies to Acinetobacter calcoaceticus Are Present in Bovine Spongiform Encephalopathy

    PubMed Central

    Tiwana, Harmale; Wilson, Clyde; Pirt, John; Cartmell, William; Ebringer, Alan

    1999-01-01

    Bovine spongiform encephalopathy (BSE) is a neurological disorder, predominantly of British cattle, which belongs to the group of transmissible spongiform encephalopathies together with Creutzfeldt-Jakob disease (CJD), kuru, and scrapie. Autoantibodies to brain neurofilaments have been previously described in patients with CJD and kuru and in sheep affected by scrapie. Spongiform-like changes have also been observed in chronic experimental allergic encephalomyelitis, at least in rabbits and guinea pigs, and in these conditions autoantibodies to myelin occur. We report here that animals with BSE have elevated levels of immunoglobulin A autoantibodies to brain components, i.e., neurofilaments (P < 0.001) and myelin (P < 0.001), as well as to Acinetobacter calcoaceticus (P < 0.001), saprophytic microbes found in soil which have sequences cross-reacting with bovine neurofilaments and myelin, but there were no antibody elevations against Agrobacterium tumefaciens or Escherichia coli. The relevance of such mucosal autoantibodies or antibacterial antibodies to the pathology of BSE and its possible link to prions requires further evaluation. PMID:10569779

  19. First Demonstration of Transmissible Spongiform Encephalopathy-associated Prion Protein (PrPTSE) in Extracellular Vesicles from Plasma of Mice Infected with Mouse-adapted Variant Creutzfeldt-Jakob Disease by in Vitro Amplification*

    PubMed Central

    Saá, Paula; Yakovleva, Oksana; de Castro, Jorge; Vasilyeva, Irina; De Paoli, Silvia H.; Simak, Jan; Cervenakova, Larisa

    2014-01-01

    The development of variant Creutzfeldt-Jakob disease (vCJD) in three recipients of non-leukoreduced red blood cells from asymptomatic donors who subsequently developed the disease has confirmed existing concerns about the possible spread of transmissible spongiform encephalopathies (TSEs) via blood products. In addition, the presence of disease-associated misfolded prion protein (PrPTSE), generally associated with infectivity, has been demonstrated in the blood of vCJD patients. However, its origin and distribution in this biological fluid are still unknown. Various studies have identified cellular prion protein (PrPC) among the protein cargo in human blood-circulating extracellular vesicles released from endothelial cells and platelets, and exosomes isolated from the conditioned media of TSE-infected cells have caused the disease when injected into experimental mice. In this study, we demonstrate the detection of PrPTSE in extracellular vesicles isolated from plasma samples collected during the preclinical and clinical phases of the disease from mice infected with mouse-adapted vCJD and confirm the presence of the exosomal marker Hsp70 in these preparations. PMID:25157106

  20. Social barriers to pathogen transmission in wild animal populations

    SciTech Connect

    Loehle, C.

    1995-03-01

    Diseases and pathogens are receiving increasing recognition as sources of mortality in animal populations. Immune system strength is clearly important in fending off pathogen attack. Physical barriers to pathogen entry are also important. Various individual behaviors are efficacious in reducing contact with diseases and pests. This paper focuses on a fourth mode of defense: social barriers to transmission. Various social behaviors have pathogen transmission consequences. Selective pressures on these social behaviors may therefore exist. Effects on pathogen transmission of mating strategies, social avoidance, group size, group isolation, and other behaviors are explored. It is concluded that many of these behaviors may have been affected by selection pressures to reduce transmission of pathogens. 84 refs., 1 tab.

  1. 77 FR 20319 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-04

    ...; ] DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service 9 CFR Part 93 RIN 0579-AC68 Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products Correction In proposed rule...

  2. Social Information Transmission in Animals: Lessons from Studies of Diffusion.

    PubMed

    Duboscq, Julie; Romano, Valéria; MacIntosh, Andrew; Sueur, Cédric

    2016-01-01

    The capacity to use information provided by others to guide behavior is a widespread phenomenon in animal societies. A standard paradigm to test if and/or how animals use and transfer social information is through social diffusion experiments, by which researchers observe how information spreads within a group, sometimes by seeding new behavior in the population. In this article, we review the context, methodology and products of such social diffusion experiments. Our major focus is the transmission of information from an individual (or group thereof) to another, and the factors that can enhance or, more interestingly, inhibit it. We therefore also discuss reasons why social transmission sometimes does not occur despite being expected to. We span a full range of mechanisms and processes, from the nature of social information itself and the cognitive abilities of various species, to the idea of social competency and the constraints imposed by the social networks in which animals are embedded. We ultimately aim at a broad reflection on practical and theoretical issues arising when studying how social information spreads within animal groups. PMID:27540368

  3. Social Information Transmission in Animals: Lessons from Studies of Diffusion

    PubMed Central

    Duboscq, Julie; Romano, Valéria; MacIntosh, Andrew; Sueur, Cédric

    2016-01-01

    The capacity to use information provided by others to guide behavior is a widespread phenomenon in animal societies. A standard paradigm to test if and/or how animals use and transfer social information is through social diffusion experiments, by which researchers observe how information spreads within a group, sometimes by seeding new behavior in the population. In this article, we review the context, methodology and products of such social diffusion experiments. Our major focus is the transmission of information from an individual (or group thereof) to another, and the factors that can enhance or, more interestingly, inhibit it. We therefore also discuss reasons why social transmission sometimes does not occur despite being expected to. We span a full range of mechanisms and processes, from the nature of social information itself and the cognitive abilities of various species, to the idea of social competency and the constraints imposed by the social networks in which animals are embedded. We ultimately aim at a broad reflection on practical and theoretical issues arising when studying how social information spreads within animal groups. PMID:27540368

  4. 76 FR 35185 - Notice of Request for Extension of Approval of an Information Collection; Bovine Spongiform...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ... Animal and Plant Health Inspection Service Notice of Request for Extension of Approval of an Information Collection; Bovine Spongiform Encephalopathy; Importation of Animals and Animal Products AGENCY: Animal and... the Animal and Plant Health Inspection Service's intention to request an extension of approval of...

  5. Mechanisms of Arthropod Transmission of Plant and Animal Viruses

    PubMed Central

    Gray, Stewart M.; Banerjee, Nanditta

    1999-01-01

    A majority of the plant-infecting viruses and many of the animal-infecting viruses are dependent upon arthropod vectors for transmission between hosts and/or as alternative hosts. The viruses have evolved specific associations with their vectors, and we are beginning to understand the underlying mechanisms that regulate the virus transmission process. A majority of plant viruses are carried on the cuticle lining of a vector’s mouthparts or foregut. This initially appeared to be simple mechanical contamination, but it is now known to be a biologically complex interaction between specific virus proteins and as yet unidentified vector cuticle-associated compounds. Numerous other plant viruses and the majority of animal viruses are carried within the body of the vector. These viruses have evolved specific mechanisms to enable them to be transported through multiple tissues and to evade vector defenses. In response, vector species have evolved so that not all individuals within a species are susceptible to virus infection or can serve as a competent vector. Not only are the virus components of the transmission process being identified, but also the genetic and physiological components of the vectors which determine their ability to be used successfully by the virus are being elucidated. The mechanisms of arthropod-virus associations are many and complex, but common themes are beginning to emerge which may allow the development of novel strategies to ultimately control epidemics caused by arthropod-borne viruses. PMID:10066833

  6. Transmission and epidemiology of zoonotic protozoal diseases of companion animals.

    PubMed

    Esch, Kevin J; Petersen, Christine A

    2013-01-01

    Over 77 million dogs and 93 million cats share our households in the United States. Multiple studies have demonstrated the importance of pets in their owners' physical and mental health. Given the large number of companion animals in the United States and the proximity and bond of these animals with their owners, understanding and preventing the diseases that these companions bring with them are of paramount importance. Zoonotic protozoal parasites, including toxoplasmosis, Chagas' disease, babesiosis, giardiasis, and leishmaniasis, can cause insidious infections, with asymptomatic animals being capable of transmitting disease. Giardia and Toxoplasma gondii, endemic to the United States, have high prevalences in companion animals. Leishmania and Trypanosoma cruzi are found regionally within the United States. These diseases have lower prevalences but are significant sources of human disease globally and are expanding their companion animal distribution. Thankfully, healthy individuals in the United States are protected by intact immune systems and bolstered by good nutrition, sanitation, and hygiene. Immunocompromised individuals, including the growing number of obese and/or diabetic people, are at a much higher risk of developing zoonoses. Awareness of these often neglected diseases in all health communities is important for protecting pets and owners. To provide this awareness, this review is focused on zoonotic protozoal mechanisms of virulence, epidemiology, and the transmission of pathogens of consequence to pet owners in the United States. PMID:23297259

  7. Transmission and Epidemiology of Zoonotic Protozoal Diseases of Companion Animals

    PubMed Central

    Esch, Kevin J.

    2013-01-01

    Over 77 million dogs and 93 million cats share our households in the United States. Multiple studies have demonstrated the importance of pets in their owners' physical and mental health. Given the large number of companion animals in the United States and the proximity and bond of these animals with their owners, understanding and preventing the diseases that these companions bring with them are of paramount importance. Zoonotic protozoal parasites, including toxoplasmosis, Chagas' disease, babesiosis, giardiasis, and leishmaniasis, can cause insidious infections, with asymptomatic animals being capable of transmitting disease. Giardia and Toxoplasma gondii, endemic to the United States, have high prevalences in companion animals. Leishmania and Trypanosoma cruzi are found regionally within the United States. These diseases have lower prevalences but are significant sources of human disease globally and are expanding their companion animal distribution. Thankfully, healthy individuals in the United States are protected by intact immune systems and bolstered by good nutrition, sanitation, and hygiene. Immunocompromised individuals, including the growing number of obese and/or diabetic people, are at a much higher risk of developing zoonoses. Awareness of these often neglected diseases in all health communities is important for protecting pets and owners. To provide this awareness, this review is focused on zoonotic protozoal mechanisms of virulence, epidemiology, and the transmission of pathogens of consequence to pet owners in the United States. PMID:23297259

  8. Critical Behavior in Cellular Automata Animal Disease Transmission Model

    NASA Astrophysics Data System (ADS)

    Morley, P. D.; Chang, Julius

    Using cellular automata model, we simulate the British Government Policy (BGP) in the 2001 foot and mouth epidemic in Great Britain. When clinical symptoms of the disease appeared in a farm, there is mandatory slaughter (culling) of all livestock in an infected premise (IP). Those farms in the neighboring of an IP (contiguous premise, CP), are also culled, aka nearest neighbor interaction. Farms where the disease may be prevalent from animal, human, vehicle or airborne transmission (dangerous contact, DC), are additionally culled, aka next-to-nearest neighbor interactions and lightning factor. The resulting mathematical model possesses a phase transition, whereupon if the physical disease transmission kernel exceeds a critical value, catastrophic loss of animals ensues. The nonlocal disease transport probability can be as low as 0.01% per day and the disease can still be in the high mortality phase. We show that the fundamental equation for sustainable disease transport is the criticality equation for neutron fission cascade. Finally, we calculate that the percentage of culled animals that are actually healthy is ≈30%.

  9. Animal models for influenza virus transmission studies: A historical perspective

    PubMed Central

    Bouvier, Nicole M.

    2015-01-01

    Animal models are used to simulate, under experimental conditions, the complex interactions among host, virus, and environment that affect the person-to-person spread of influenza viruses. The three species that have been most frequently employed, both past and present, as influenza virus transmission models -- ferrets, mice, and guinea pigs -- have each provided unique insights into the factors governing the efficiency with which these viruses pass from an infected host to a susceptible one. This review will highlight a few of these noteworthy discoveries, with a particular focus on the historical contexts in which each model was developed and the advantages and disadvantages of each species with regard to the study of influenza virus transmission among mammals. PMID:26126082

  10. Bovine Spongiform Encephalopathy Infectivity in Greater Kudu (Tragelaphus strepsiceros)

    PubMed Central

    Kirkwood, James K.; Dawson, Michael; Spencer, Yvonne I.; Green, Robert B.; Wells, Gerald A.H.

    2004-01-01

    Of all the species exposed naturally to the bovine spongiform encephalopathy (BSE) agent, the greater kudu (Tragelaphus strepsiceros), a nondomesticated bovine from Africa, appears to be the most susceptible to the disease. We present the results of mouse bioassay studies to show that, contrary to findings in cattle with BSE in which the tissue distribution of infectivity is the most limited recorded for any of the transmissible spongiform encephalopathies (TSE), infectivity in greater kudu with BSE is distributed in as wide a range of tissues as occurs in any TSE. BSE agent was also detected in skin, conjunctiva, and salivary gland, tissues in which infectivity has not previously been reported in any naturally occurring TSE. The distribution of infectivity in greater kudu with BSE suggests possible routes for transmission of the disease and highlights the need for further research into the distribution of TSE infectious agents in other host species. PMID:15207051

  11. PRIONS AND THE TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

    EPA Science Inventory

    This book chapter is an invited, scholarly review of the mechanism(s) of TSEs for the 2nd edition of Metabolic Encephalopathies. Each chapter in the book assumes a professional knowledge of neuroscience and biochemistry, and the focus of the book is on the metabolic basis of dise...

  12. Central nervous system gene expression changes in a transgenic mouse model for bovine spongiform encephalopathy

    PubMed Central

    2011-01-01

    Gene expression analysis has proven to be a very useful tool to gain knowledge of the factors involved in the pathogenesis of diseases, particularly in the initial or preclinical stages. With the aim of finding new data on the events occurring in the Central Nervous System in animals affected with Bovine Spongiform Encephalopathy, a comprehensive genome wide gene expression study was conducted at different time points of the disease on mice genetically modified to model the bovine species brain in terms of cellular prion protein. An accurate analysis of the information generated by microarray technique was the key point to assess the biological relevance of the data obtained in terms of Transmissible Spongiform Encephalopathy pathogenesis. Validation of the microarray technique was achieved by RT-PCR confirming the RNA change and immunohistochemistry techniques that verified that expression changes were translated into variable levels of protein for selected genes. Our study reveals changes in the expression of genes, some of them not previously associated with prion diseases, at early stages of the disease previous to the detection of the pathological prion protein, that might have a role in neuronal degeneration and several transcriptional changes showing an important imbalance in the Central Nervous System homeostasis in advanced stages of the disease. Genes whose expression is altered at early stages of the disease should be considered as possible therapeutic targets and potential disease markers in preclinical diagnostic tool development. Genes non-previously related to prion diseases should be taken into consideration for further investigations. PMID:22035425

  13. [Creutzfeldt-Jakob disease: the most frequent spongiform encephalopathy in humans].

    PubMed

    Kulczycki, J

    2001-01-01

    Creutzfeldt-Jakob disease (CJD) which for many years was interpreted as one of degenerative brain processes is the most frequent spongiform encephalopathy caused by prions--molecules of erroneously conformed protein. In only few percent ill people occurrence of this pathogenic factor occurs as a result of mutation in gene PrP. Because transmissibility of prions was proved it should be supposed that in other cases CJD is a result of "infection" Susceptibility to prions depends in large part on specificity of host proteins. It creates certain individual and species specific barriers. At the present time we witness, fortunately only in single cases, occurrence in people variant CJD caused by prions originated from animals affected by "mad cow disease". Prognosis for human population is dependent on the effectiveness of between species barrier for prions. PMID:11556078

  14. [Animal mites transmissible to humans and associated zoonosis].

    PubMed

    Jofré M, Leonor; Noemí H, Isabel; Neira O, Patricia; Saavedra U, Tirza; Díaz L, Cecilia

    2009-06-01

    Mites that affect animals (acariasis) can occasionally be transmitted to humans by incidental contact producing pruritus and dermatitis. Animals such as dogs, cats, mice, birds and reptiles, harbour several mite species. Hemophage mites and those that feed on lymph have the potential of transmitting important zoonotic agents (cuales??). The presence of lesions of unclear origin and a history of contact with pets or wild animals should alert towards the possibility of acariasis. Diagnosis is based on direct visualization of the mite,analysis of its morphology and obtaining information on the animal host. Awareness of these acarosis and the responsible care of pets and animals are the most relevant preventive measures. PMID:19621159

  15. SPONGIFORM DISEASE: Experts Downplay New vCJD Fears.

    PubMed

    Balter, M

    2000-09-01

    The chilling scenario of getting "mad cow disease" from eating products of other animals besides just cows was splashed across the mainstream British press last week based on a report from a leading U.K. lab that prions--abnormal proteins linked to bovine spongiform encephalopathy and its human form, variant Creutzfeldt-Jakob disease--can jump from one species to another more easily than previously believed. Although some experts say the findings raise concern about a threat to human health, others decry the media frenzy and contend that the new research adds little to what is known about the mysterious, fatal diseases. PMID:17811144

  16. Cattle traceability system in Japan for bovine spongiform encephalopathy.

    PubMed

    Sugiura, Katsuaki; Onodera, Takashi

    2008-01-01

    To promote consumer confidence in the safety of beef and to ensure the proper implementation of eradication measures against bovine spongiform encephalopathy (BSE), the Cattle Traceability Law was approved by the Diet in June 2003 and a cattle traceability system has been in operation in Japan since December 2003. The system enables tracing the cohort and offspring animals of a BSE case within 24 h of its detection. The traceability database system also provides distributors, restaurants and consumers with information on the cattle from which the beef that they sell, serve and consume, originate. PMID:20405448

  17. Transmission of Avian Influenza A Viruses Between Animals and People

    MedlinePlus

    ... many different animals, including ducks, chickens, pigs, whales, horses, and seals. However, certain subtypes of influenza A ... pigs, and H7N7 and H3N8 virus infections of horses. Influenza A viruses that typically infect and transmit ...

  18. Multilevel animal societies can emerge from cultural transmission.

    PubMed

    Cantor, Maurício; Shoemaker, Lauren G; Cabral, Reniel B; Flores, César O; Varga, Melinda; Whitehead, Hal

    2015-01-01

    Multilevel societies, containing hierarchically nested social levels, are remarkable social structures whose origins are unclear. The social relationships of sperm whales are organized in a multilevel society with an upper level composed of clans of individuals communicating using similar patterns of clicks (codas). Using agent-based models informed by an 18-year empirical study, we show that clans are unlikely products of stochastic processes (genetic or cultural drift) but likely originate from cultural transmission via biased social learning of codas. Distinct clusters of individuals with similar acoustic repertoires, mirroring the empirical clans, emerge when whales learn preferentially the most common codas (conformism) from behaviourally similar individuals (homophily). Cultural transmission seems key in the partitioning of sperm whales into sympatric clans. These findings suggest that processes similar to those that generate complex human cultures could not only be at play in non-human societies but also create multilevel social structures in the wild. PMID:26348688

  19. Multilevel animal societies can emerge from cultural transmission

    PubMed Central

    Cantor, Maurício; Shoemaker, Lauren G.; Cabral, Reniel B.; Flores, César O.; Varga, Melinda; Whitehead, Hal

    2015-01-01

    Multilevel societies, containing hierarchically nested social levels, are remarkable social structures whose origins are unclear. The social relationships of sperm whales are organized in a multilevel society with an upper level composed of clans of individuals communicating using similar patterns of clicks (codas). Using agent-based models informed by an 18-year empirical study, we show that clans are unlikely products of stochastic processes (genetic or cultural drift) but likely originate from cultural transmission via biased social learning of codas. Distinct clusters of individuals with similar acoustic repertoires, mirroring the empirical clans, emerge when whales learn preferentially the most common codas (conformism) from behaviourally similar individuals (homophily). Cultural transmission seems key in the partitioning of sperm whales into sympatric clans. These findings suggest that processes similar to those that generate complex human cultures could not only be at play in non-human societies but also create multilevel social structures in the wild. PMID:26348688

  20. A model of animal-human brucellosis transmission in Mongolia.

    PubMed

    Zinsstag, J; Roth, F; Orkhon, D; Chimed-Ochir, G; Nansalmaa, M; Kolar, J; Vounatsou, P

    2005-06-10

    We developed a dynamic model of livestock-to-human brucellosis transmission in Mongolia. The compartmental model considers transmission within sheep and cattle populations and the transmission to humans as additive components. The model was fitted to demographic and seroprevalence data (Rose Bengal test) from livestock and annually reported new human brucellosis cases in Mongolia for 1991-1999 prior to the onset of a mass livestock-vaccination campaign (S19 Brucella abortus for cattle and Rev 1 Brucella melitensis for sheep and goat). The vaccination effect was fitted to livestock- and human-brucellosis data from the first 3 years of the vaccination campaign (2000-2002). Parameters were optimized on the basis of the goodness-of-fit (assessed by the deviance). The simultaneously fitted sheep-human and cattle-human contact rates show that 90% of human brucellosis was small-ruminant derived. Average effective reproductive ratios for the year 1999 were 1.2 for sheep and 1.7 for cattle. PMID:15899298

  1. Insights into Chronic Wasting Disease and Bovine Spongiform Encephalopathy Species Barriers by Use of Real-Time Conversion

    PubMed Central

    Davenport, Kristen A.; Henderson, Davin M.; Bian, Jifeng; Telling, Glenn C.; Mathiason, Candace K.

    2015-01-01

    ABSTRACT The propensity for transspecies prion transmission is related to the structural characteristics of the enciphering and new host PrP, although the exact mechanism remains incompletely understood. The effects of variability in prion protein on cross-species prion transmission have been studied with animal bioassays, but the influence of prion protein structure versus that of host cofactors (e.g., cellular constituents, trafficking, and innate immune interactions) remains difficult to dissect. To isolate the effects of protein-protein interactions on transspecies conversion, we used recombinant PrPC and real-time quaking-induced conversion (RT-QuIC) and compared chronic wasting disease (CWD) and classical bovine spongiform encephalopathy (cBSE) prions. To assess the impact of transmission to a new species, we studied feline CWD (fCWD) and feline BSE (i.e., feline spongiform encephalopathy [FSE]). We cross-seeded fCWD and FSE into each species' full-length, recombinant PrPC and measured the time required for conversion to the amyloid (PrPRes) form, which we describe here as the rate of amyloid conversion. These studies revealed the following: (i) CWD and BSE seeded their homologous species' PrP best; (ii) fCWD was a more efficient seed for feline rPrP than for white-tailed deer rPrP; (iii) conversely, FSE more efficiently converted bovine than feline rPrP; (iv) and CWD, fCWD, BSE, and FSE all converted human rPrP, although not as efficiently as homologous sCJD prions. These results suggest that (i) at the level of protein-protein interactions, CWD adapts to a new species more readily than does BSE and (ii) the barrier preventing transmission of CWD to humans may be less robust than estimated. IMPORTANCE We demonstrate that bovine spongiform encephalopathy prions maintain their transspecies conversion characteristics upon passage to cats but that chronic wasting disease prions adapt to the cat and are distinguishable from the original prion. Additionally, we

  2. 78 FR 72859 - Concurrence With OIE Risk Designations for Bovine Spongiform Encephalopathy

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-04

    ... spongiform encephalopathy (BSE) risk designations for 14 regions. The OIE recognizes these regions as being of either negligible risk for BSE or of controlled risk for BSE. We are taking this action based on... Animal and Plant Health Inspection Service Concurrence With OIE Risk Designations for Bovine...

  3. Cell-Associated Transmission of HIV Type 1 and Other Lentiviruses in Small-Animal Models

    PubMed Central

    Moench, Thomas R.

    2014-01-01

    Small-animal models of lentivirus transmission have repeatedly demonstrated transmission by cell-associated virus via vaginal, rectal, and oral routes. The earliest experiments were in the cat/feline immunodeficiency virus model, followed a decade later by successful vaginal transmission of cell-associated human immunodeficiency virus (HIV) in mice bearing transplanted human immune cells. After early unsuccessful attempts at cell-associated transmission in nonhuman primates, renewed investigation in diverse primate models has now confirmed the findings from the cat and humanized mouse models. Improvements in humanized mouse models have made them the preferred small-animal models to study HIV mucosal transmission. They provide complementary systems to nonhuman primate models to aid in the elucidation of the many remaining questions on the mechanism of and means to prevent both cell-associated and cell-free HIV transmission across mucosal barriers. PMID:25414420

  4. Animal models for influenza virus pathogenesis, transmission, and immunology

    PubMed Central

    Thangavel, Rajagowthamee R.; Bouvier, Nicole M.

    2014-01-01

    In humans, infection with an influenza A or B virus manifests typically as an acute and self-limited upper respiratory tract illness characterized by fever, cough, sore throat, and malaise. However, influenza can present along a broad spectrum of disease, ranging from sub-clinical or even asymptomatic infection to a severe primary viral pneumonia requiring advanced medical supportive care. Disease severity depends upon the virulence of the influenza virus strain and the immune competence and previous influenza exposures of the patient. Animal models are used in influenza research not only to elucidate the viral and host factors that affect influenza disease outcomes in and spread among susceptible hosts, but also to evaluate interventions designed to prevent or reduce influenza morbidity and mortality in man. This review will focus on the three animal models currently used most frequently in influenza virus research -- mice, ferrets, and guinea pigs -- and discuss the advantages and disadvantages of each. PMID:24709389

  5. Identifying Transmission Cycles at the Human-Animal Interface: The Role of Animal Reservoirs in Maintaining Gambiense Human African Trypanosomiasis

    PubMed Central

    Funk, Sebastian; Nishiura, Hiroshi; Heesterbeek, Hans; Edmunds, W. John; Checchi, Francesco

    2013-01-01

    Many infections can be transmitted between animals and humans. The epidemiological roles of different species can vary from important reservoirs to dead-end hosts. Here, we present a method to identify transmission cycles in different combinations of species from field data. We used this method to synthesise epidemiological and ecological data from Bipindi, Cameroon, a historical focus of gambiense Human African Trypanosomiasis (HAT, sleeping sickness), a disease that has often been considered to be maintained mainly by humans. We estimated the basic reproduction number of gambiense HAT in Bipindi and evaluated the potential for transmission in the absence of human cases. We found that under the assumption of random mixing between vectors and hosts, gambiense HAT could not be maintained in this focus without the contribution of animals. This result remains robust under extensive sensitivity analysis. When using the distributions of species among habitats to estimate the amount of mixing between those species, we found indications for an independent transmission cycle in wild animals. Stochastic simulation of the system confirmed that unless vectors moved between species very rarely, reintroduction would usually occur shortly after elimination of the infection from human populations. This suggests that elimination strategies may have to be reconsidered as targeting human cases alone would be insufficient for control, and reintroduction from animal reservoirs would remain a threat. Our approach is broadly applicable and could reveal animal reservoirs critical to the control of other infectious diseases. PMID:23341760

  6. The role of dipterous insects in the mechanical transmission of animal viruses.

    PubMed

    Carn, V M

    1996-07-01

    Animals viruses may be transmitted by arthropods in two ways, either biologically or mechanically. Many different species of Diptera are implicated in mechanical transmission, but haematophagous species are the most important. The insects become contaminated with virus during normal feeding behaviour, and virus persists on their mouthparts or body until the next feed. Some viruses are inactivated rapidly on mouthparts, whereas others survive for many days or weeks, prolonging the potential period of transmission. Some viruses produce high titres in the skin of the infected vertebrate host, which facilitates transmission, whereas other viruses are transmitted even during relatively low levels of viraemia. Mechanical transmission by arthropods is important in the epidemiology of many animal diseases, and may be the major mode of horizontal transmission. In other instances vector spread is merely incidental. PMID:8791847

  7. Turbulent dispersivity under conditions relevant to airborne disease transmission between laboratory animals

    NASA Astrophysics Data System (ADS)

    Halloran, Siobhan; Wexler, Anthony; Ristenpart, William

    2014-11-01

    Virologists and other researchers who test pathogens for airborne disease transmissibility often place a test animal downstream from an inoculated animal and later determine whether the test animal became infected. Despite the crucial role of the airflow in modulating the pathogen transmission, to date the infectious disease community has paid little attention to the effect of airspeed or turbulence intensity on the probability of transmission. Here we present measurements of the turbulent dispersivity under conditions relevant to experimental tests of airborne disease transmissibility between laboratory animals. We used time lapse photography to visualize the downstream transport and turbulent dispersion of smoke particulates released from a point source downstream of a standard axial fan, thus mimicking the release and transport of expiratory aerosols exhaled by an inoculated animal. We demonstrate that the fan speed counterintuitively has no effect on the downstream plume width, a result replicated with a variety of different fan types and configurations. The results point toward a useful simplification in modeling of airborne disease transmission via fan-generated flows.

  8. The epidemics of bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: current status and future prospects.

    PubMed Central

    Smith, Peter G.

    2003-01-01

    The large epidemic of bovine spongiform encephalopathy (BSE) in the United Kingdom has been in decline since 1992, but has spread to other countries. The extensive control measures that have been put in place across the European Union and also in Switzerland should have brought the transmission of BSE under control in these countries, provided that the measures were properly enforced. Postmortem tests on brain tissue enable infected animals to be detected during the late stages of the incubation period, but tests that can be performed on live animals (including humans) and that will detect infections early are urgently needed. The number of infected animals currently entering the food chain is probably small, and the controls placed on bovine tissues in the European Union and Switzerland should ensure that any risks to human health are small and diminishing. Vigilance is required in all countries, especially in those in which there has been within-species recycling of ruminant feed. Fewer than 150 people, globally, have been diagnosed with variant Creutzfeldt-Jakob disease (vCJD), but there are many uncertainties about the future course of the epidemic because of the long and variable incubation period. Better control measures are necessary to guard against the possibility of iatrogenic transmission through blood transfusion or contaminated surgical instruments. These measures will required sensitive and specific, diagnostic tests and improved decontamination methods. PMID:12751420

  9. Implications of Heterogeneous Biting Exposure and Animal Hosts on Trypanosomiasis brucei gambiense Transmission and Control.

    PubMed

    Stone, Chris M; Chitnis, Nakul

    2015-10-01

    The gambiense form of sleeping sickness is a neglected tropical disease, which is presumed to be anthroponotic. However, the parasite persists in human populations at levels of considerable rarity and as such the existence of animal reservoirs has been posited. Clarifying the impact of animal host reservoirs on the feasibility of interrupting sleeping sickness transmission through interventions is a matter of urgency. We developed a mathematical model allowing for heterogeneous exposure of humans to tsetse, with animal populations that differed in their ability to transmit infections, to investigate the effectiveness of two established techniques, screening and treatment of at-risk populations, and vector control. Importantly, under both assumptions, an integrated approach of human screening and vector control was supported in high transmission areas. However, increasing the intensity of vector control was more likely to eliminate transmission, while increasing the intensity of human screening reduced the time to elimination. Non-human animal hosts played important, but different roles in HAT transmission, depending on whether or not they contributed as reservoirs. If they did not serve as reservoirs, sensitivity analyses suggested their attractiveness may instead function as a sink for tsetse bites. These outcomes highlight the importance of understanding the ecological and environmental context of sleeping sickness in optimizing integrated interventions, particularly for moderate and low transmission intensity settings. PMID:26426854

  10. Implications of Heterogeneous Biting Exposure and Animal Hosts on Trypanosomiasis brucei gambiense Transmission and Control

    PubMed Central

    Stone, Chris M.; Chitnis, Nakul

    2015-01-01

    The gambiense form of sleeping sickness is a neglected tropical disease, which is presumed to be anthroponotic. However, the parasite persists in human populations at levels of considerable rarity and as such the existence of animal reservoirs has been posited. Clarifying the impact of animal host reservoirs on the feasibility of interrupting sleeping sickness transmission through interventions is a matter of urgency. We developed a mathematical model allowing for heterogeneous exposure of humans to tsetse, with animal populations that differed in their ability to transmit infections, to investigate the effectiveness of two established techniques, screening and treatment of at-risk populations, and vector control. Importantly, under both assumptions, an integrated approach of human screening and vector control was supported in high transmission areas. However, increasing the intensity of vector control was more likely to eliminate transmission, while increasing the intensity of human screening reduced the time to elimination. Non-human animal hosts played important, but different roles in HAT transmission, depending on whether or not they contributed as reservoirs. If they did not serve as reservoirs, sensitivity analyses suggested their attractiveness may instead function as a sink for tsetse bites. These outcomes highlight the importance of understanding the ecological and environmental context of sleeping sickness in optimizing integrated interventions, particularly for moderate and low transmission intensity settings. PMID:26426854

  11. Transient fecal shedding and limited animal-to-animal transmission of Clostridium difficile by naturally infected finishing feedlot cattle.

    PubMed

    Rodriguez-Palacios, Alexander; Pickworth, Carrie; Loerch, Steve; LeJeune, Jeffrey T

    2011-05-01

    To longitudinally assess fecal shedding and animal-to-animal transmission of Clostridium difficile among finishing feedlot cattle as a risk for beef carcass contamination, we tested 186 ± 12 steers (mean ± standard deviation; 1,369 samples) in an experimental feedlot facility during the finishing period and at harvest. Clostridium difficile was isolated from 12.9% of steers on arrival (24/186; 0 to 33% among five suppliers). Shedding decreased to undetectable levels a week later (0%; P < 0.001), and remained low (< 3.6%) until immediately prior to shipment for harvest (1.2%). Antimicrobial use did not increase fecal shedding, despite treatment of 53% of animals for signs of respiratory disease. Animals shedding C. difficile on arrival, however, had 4.6 times higher odds of receiving antimicrobials for respiratory signs than nonshedders (95% confidence interval for the odds ratio, 1.4 to 14.8; P = 0.01). Neither the toxin genes nor toxin A or B was detected in most (39/42) isolates based on two complementary multiplex PCRs and enzyme-linked immunosorbent assay testing, respectively. Two linezolid- and clindamycin-resistant PCR ribotype 078 (tcdA+/tcdB+/cdtB+/39-bp-type deletion in tcdC) isolates were identified from two steers (at arrival and week 20), but these ribotypes did not become endemic. The other toxigenic isolate (tcdA+/tcdB+/cdtB+/classic tcdC; PCR ribotype 078-like) was identified in the cecum of one steer at harvest. Spatio-temporal analysis indicated transient shedding with no evidence of animal-to-animal transmission. The association between C. difficile shedding upon arrival and the subsequent need for antimicrobials for respiratory disease might indicate common predisposing factors. The isolation of toxigenic C. difficile from bovine intestines at harvest highlights the potential for food contamination in meat processing plants. PMID:21441320

  12. Monkeypox disease transmission in an experimental setting: prairie dog animal model.

    PubMed

    Hutson, Christina L; Carroll, Darin S; Gallardo-Romero, Nadia; Weiss, Sonja; Clemmons, Cody; Hughes, Christine M; Salzer, Johanna S; Olson, Victoria A; Abel, Jason; Karem, Kevin L; Damon, Inger K

    2011-01-01

    Monkeypox virus (MPXV) is considered the most significant human public health threat in the genus Orthopoxvirus since the eradication of variola virus (the causative agent of smallpox). MPXV is a zoonotic agent endemic to forested areas of Central and Western Africa. In 2003, MPXV caused an outbreak in the United States due to the importation of infected African rodents, and subsequent sequential infection of North American prairie dogs (Cynomys ludovicianus) and humans. In previous studies, the prairie dog MPXV model has successfully shown to be very useful for understanding MPXV since the model emulates key characteristics of human monkeypox disease. In humans, percutaneous exposure to animals has been documented but the primary method of human-to-human MPXV transmission is postulated to be by respiratory route. Only a few animal model studies of MPXV transmission have been reported. Herein, we show that MPXV infected prairie dogs are able to transmit the virus to naive animals through multiple transmission routes. All secondarily exposed animals were infected with MPXV during the course of the study. Notably, animals secondarily exposed appeared to manifest more severe disease; however, the disease course was very similar to those of experimentally challenged animals including inappetence leading to weight loss, development of lesions, production of orthopoxvirus antibodies and shedding of similar levels or in some instances higher levels of MPXV from the oral cavity. Disease was transmitted via exposure to contaminated bedding, co-housing, or respiratory secretions/nasal mucous (we could not definitively say that transmission occurred via respiratory route exclusively). Future use of the model will allow us to evaluate infection control measures, vaccines and antiviral strategies to decrease disease transmission. PMID:22164263

  13. Animal models of disease shed light on Nipah virus pathogenesis and transmission

    PubMed Central

    de Wit, Emmie; Munster, Vincent J.

    2014-01-01

    Nipah virus is an emerging virus infection that causes yearly disease outbreaks with high case fatality rates in Bangladesh. Nipah virus causes encephalitis and systemic vasculitis, sometimes in combination with respiratory disease. Pteropus species fruit bats are the natural reservoir of Nipah virus and zoonotic transmission can occur directly or via an intermediate host; human-to-human transmission occurs regularly. In this review we discuss the current state of knowledge on the pathogenesis and transmission of Nipah virus, focusing on dissemination of the virus through its host, known determinants of pathogenicity and routes of zoonotic and human-to-human transmission. Since data from human cases are sparse, this knowledge is largely based on the results of studies performed in animal models that recapitulate Nipah virus disease in humans. PMID:25229234

  14. Whole Blood Gene Expression Profiling in Preclinical and Clinical Cattle Infected with Atypical Bovine Spongiform Encephalopathy.

    PubMed

    Xerxa, Elena; Barbisin, Maura; Chieppa, Maria Novella; Krmac, Helena; Vallino Costassa, Elena; Vatta, Paolo; Simmons, Marion; Caramelli, Maria; Casalone, Cristina; Corona, Cristiano; Legname, Giuseppe

    2016-01-01

    Prion diseases, such as bovine spongiform encephalopathies (BSE), are transmissible neurodegenerative disorders affecting humans and a wide variety of mammals. Variant Creutzfeldt-Jakob disease (vCJD), a prion disease in humans, has been linked to exposure to BSE prions. This classical BSE (cBSE) is now rapidly disappearing as a result of appropriate measures to control animal feeding. Besides cBSE, two atypical forms (named H- and L-type BSE) have recently been described in Europe, Japan, and North America. Here we describe the first wide-spectrum microarray analysis in whole blood of atypical BSE-infected cattle. Transcriptome changes in infected animals were analyzed prior to and after the onset of clinical signs. The microarray analysis revealed gene expression changes in blood prior to the appearance of the clinical signs and during the progression of the disease. A set of 32 differentially expressed genes was found to be in common between clinical and preclinical stages and showed a very similar expression pattern in the two phases. A 22-gene signature showed an oscillating pattern of expression, being differentially expressed in the preclinical stage and then going back to control levels in the symptomatic phase. One gene, SEL1L3, was downregulated during the progression of the disease. Most of the studies performed up to date utilized various tissues, which are not suitable for a rapid analysis of infected animals and patients. Our findings suggest the intriguing possibility to take advantage of whole blood RNA transcriptional profiling for the preclinical identification of prion infection. Further, this study highlighted several pathways, such as immune response and metabolism that may play an important role in peripheral prion pathogenesis. Finally, the gene expression changes identified in the present study may be further investigated as a fingerprint for monitoring the progression of disease and for developing targeted therapeutic interventions. PMID

  15. Whole Blood Gene Expression Profiling in Preclinical and Clinical Cattle Infected with Atypical Bovine Spongiform Encephalopathy

    PubMed Central

    Xerxa, Elena; Barbisin, Maura; Chieppa, Maria Novella; Krmac, Helena; Vallino Costassa, Elena; Vatta, Paolo; Simmons, Marion; Caramelli, Maria; Casalone, Cristina; Corona, Cristiano

    2016-01-01

    Prion diseases, such as bovine spongiform encephalopathies (BSE), are transmissible neurodegenerative disorders affecting humans and a wide variety of mammals. Variant Creutzfeldt-Jakob disease (vCJD), a prion disease in humans, has been linked to exposure to BSE prions. This classical BSE (cBSE) is now rapidly disappearing as a result of appropriate measures to control animal feeding. Besides cBSE, two atypical forms (named H- and L-type BSE) have recently been described in Europe, Japan, and North America. Here we describe the first wide-spectrum microarray analysis in whole blood of atypical BSE-infected cattle. Transcriptome changes in infected animals were analyzed prior to and after the onset of clinical signs. The microarray analysis revealed gene expression changes in blood prior to the appearance of the clinical signs and during the progression of the disease. A set of 32 differentially expressed genes was found to be in common between clinical and preclinical stages and showed a very similar expression pattern in the two phases. A 22-gene signature showed an oscillating pattern of expression, being differentially expressed in the preclinical stage and then going back to control levels in the symptomatic phase. One gene, SEL1L3, was downregulated during the progression of the disease. Most of the studies performed up to date utilized various tissues, which are not suitable for a rapid analysis of infected animals and patients. Our findings suggest the intriguing possibility to take advantage of whole blood RNA transcriptional profiling for the preclinical identification of prion infection. Further, this study highlighted several pathways, such as immune response and metabolism that may play an important role in peripheral prion pathogenesis. Finally, the gene expression changes identified in the present study may be further investigated as a fingerprint for monitoring the progression of disease and for developing targeted therapeutic interventions. PMID

  16. Social and behavioral barriers to pathogen transmission in wild animal populations

    SciTech Connect

    Loehle, C.S.

    1988-12-31

    Disease and pathogens have been studied as regulators of animal populations but not really as selective forces. The authors propose that pathogens can be major selective forces influencing social behaviors when these are successful at reducing disease transmission. The behaviors whose evolution could have been influenced by pathogen effects include group size, group isolation, mixed species flocking, migration, seasonal sociality, social avoidance, and dominance behaviors. Mate choice, mating system, and sexual selection are put in a new light when examined in terms of disease transmission. It is concluded that pathogen avoidance is a more powerful selective force than has heretofore been recognized.

  17. Fluorescence Spectroscopy of the Retina for the Screening of Bovine Spongiform Encephalopathy.

    PubMed

    Bhattacharjee, Ujjal; Graham, Catherine; Czub, Stefanie; Dudas, Sandor; Rasmussen, Mark A; Casey, Thomas A; Petrich, Jacob W

    2016-01-13

    Transmissible spongiform encephalopathies (TSE) are progressive, neurodegenerative disorders, of which bovine spongiform encephalopathy (BSE) is of special concern because it is infectious and debilitating to humans. The possibility of using fluorescence spectroscopy to screen for BSE in cattle was explored. Fluorescence spectra from the retinas of experimentally infected BSE-positive cattle with clinical disease were compared with those from both sham-inoculated and non-inoculated BSE-negative cattle. The distinct intensity difference of about 4-10-fold between the spectra of the BSE-positive and the BSE-negative (sham-inoculated and non-inoculated) eyes suggests the basis for a means of developing a rapid, noninvasive examination of BSE in particular and TSEs in general. PMID:26623498

  18. Hepatitis E vaccine immunization for rabbits to prevent animal HEV infection and zoonotic transmission.

    PubMed

    Zhang, Yulin; Zeng, Hang; Liu, Peng; Liu, Lin; Xia, Junke; Wang, Lin; Zou, Qinghua; Wang, Ling; Zhuang, Hui

    2015-09-11

    Hepatitis E virus (HEV) infection has become a significant global public health concern as increasing cases of acute and chronic hepatitis E are reported. HEV of animal origin was proved to be a possible source of human infection and a previous study showed that the recent licensed HEV 239 vaccine can serve as a candidate vaccine to manage animal sources of HEV infection. However, previous immunization strategy for rabbits was the same as that for human, which is too costly to conduct large-scale animal vaccination. In an effort to reduce the costs, three vaccination schemes were assessed in the present study. Forty specific pathogen-free (SPF) rabbits were divided randomly into five groups with eight animals for each and inoculated intramuscularly with different doses of HEV 239 and placebo, respectively. All animals were challenged intravenously with swine HEV-4 and rabbit HEV of different titers 7 weeks after the initial immunization and then fecal virus excretion was monitored for 10 weeks. The results indicated that immunizing rabbits with two 10μg doses of the vaccine is superior to vaccination with two 20μg doses or a single 30μg dose, which can protect rabbits against homologous and heterologous HEV infection. These findings could enable implementation of large-scale animal vaccination to prevent rabbit HEV infection and zoonotic transmission. PMID:26212003

  19. Arranging the bouquet of disease: floral traits and the transmission of plant and animal pathogens.

    PubMed

    McArt, Scott H; Koch, Hauke; Irwin, Rebecca E; Adler, Lynn S

    2014-05-01

    Several floral microbes are known to be pathogenic to plants or floral visitors such as pollinators. Despite the ecological and economic importance of pathogens deposited in flowers, we often lack a basic understanding of how floral traits influence disease transmission. Here, we provide the first systematic review regarding how floral traits attract vectors (for plant pathogens) or hosts (for animal pathogens), mediate disease establishment and evolve under complex interactions with plant mutualists that can be vectors for microbial antagonists. Attraction of floral visitors is influenced by numerous phenological, morphological and chemical traits, and several plant pathogens manipulate floral traits to attract vectors. There is rapidly growing interest in how floral secondary compounds and antimicrobial enzymes influence disease establishment in plant hosts. Similarly, new research suggests that consumption of floral secondary compounds can reduce pathogen loads in animal pollinators. Given recent concerns about pollinator declines caused in part by pathogens, the role of floral traits in mediating pathogen transmission is a key area for further research. We conclude by discussing important implications of floral transmission of pathogens for agriculture, conservation and human health, suggesting promising avenues for future research in both basic and applied biology. PMID:24528408

  20. Endoplasmic Reticulum Stress Is a Determinant of Retrovirus-Induced Spongiform Neurodegeneration

    PubMed Central

    Dimcheff, Derek E.; Askovic, Srdjan; Baker, Audrey H.; Johnson-Fowler, Cedar; Portis, John L.

    2003-01-01

    FrCasE is a mouse retrovirus that causes a fatal noninflammatory spongiform neurodegenerative disease with pathological features strikingly similar to those induced by transmissible spongiform encephalopathy (TSE) agents. Neurovirulence is determined by the sequence of the viral envelope protein, though the specific role of this protein in disease pathogenesis is not known. In the present study, we compared host gene expression in the brain stems of mice infected with either FrCasE or the avirulent virus F43, differing from FrCasE in the sequence of the envelope gene. Four of the 12 disease-specific transcripts up-regulated during the preclinical period represent responses linked to the accumulation of unfolded proteins in the endoplasmic reticulum (ER). Among these genes was CHOP/GADD153, which is induced in response to conditions that perturb endoplasmic reticulum function. In vitro studies with NIH 3T3 cells revealed up-regulation of CHOP as well as BiP, calreticulin, and Grp58/ERp57 in cells infected with FrCasE but not with F43. Immunoblot analysis of infected NIH 3T3 cells demonstrated the accumulation of uncleaved envelope precursor protein in FrCasE- but not F43-infected cells, consistent with ER retention. These results suggest that retrovirus-induced spongiform neurodegeneration represents a protein-folding disease and thus may provide a useful tool for exploring the causal link between protein misfolding and the cytopathology that it causes. PMID:14610184

  1. Possible cross-species transmission of circoviruses and cycloviruses among farm animals.

    PubMed

    Li, Linlin; Shan, Tongling; Soji, Oderinde Bamidele; Alam, Muhammad Masroor; Kunz, Thomas H; Zaidi, Sohail Zahoor; Delwart, Eric

    2011-04-01

    Circoviruses consist of highly prevalent and genetically diverse porcine and avian pathogens. The genomes of cycloviruses, a proposed new genus in the family Circoviridae, were recently identified in human and chimpanzee faeces. Here, six cyclovirus and four circovirus genomes from the tissues of chickens, goats, cows, and a bat were amplified and sequenced using rolling-circle amplification and inverse PCR. A goat cyclovirus was nearly identical to a cyclovirus from a cow. USA beef contained circoviruses with >99% similarity to porcine circovirus 2b. Circoviruses in chicken were related to those of pigeons. The close genetic similarity of a subset of cycloviruses and circoviruses replicating in distinct animal species may reflect recent cross-species transmissions. Further studies will be required to determine the impact of these highly prevalent infections on the health of farm animals. PMID:21177928

  2. Potential role of pet animals in household transmission of methicillin-resistant Staphylococcus aureus: a narrative review.

    PubMed

    Bramble, Manuel; Morris, Daniel; Tolomeo, Pam; Lautenbach, Ebbing

    2011-06-01

    In this narrative review, we found numerous reports suggesting that dogs and cats may play a role in household methicillin-resistant Staphylococcus aureus (MRSA) transmission and recurrent MRSA infection in human contacts. Future work should emphasize elucidating more clearly the prevalence of MRSA in household pets and characterize transmission dynamics of MRSA humans and pet animals. PMID:21142959

  3. Potential Role of Pet Animals in Household Transmission of Methicillin-Resistant Staphylococcus aureus: A Narrative Review

    PubMed Central

    Bramble, Manuel; Morris, Daniel; Tolomeo, Pam

    2011-01-01

    Abstract In this narrative review, we found numerous reports suggesting that dogs and cats may play a role in household methicillin-resistant Staphylococcus aureus (MRSA) transmission and recurrent MRSA infection in human contacts. Future work should emphasize elucidating more clearly the prevalence of MRSA in household pets and characterize transmission dynamics of MRSA humans and pet animals. PMID:21142959

  4. Population-Level Retrospective Study of Neurologically Expressed Disorders in Ruminants before the Onset of Bovine Spongiform Encephalopathy (BSE) in Belgium, a BSE Risk III Country

    PubMed Central

    Saegerman, C.; Berkvens, D.; Claes, L.; Dewaele, A.; Coignoul, F.; Ducatelle, R.; Cassart, D.; Brochier, B.; Costy, F.; Roels, S.; Deluyker, H.; Vanopdenbosch, E.; Thiry, E.

    2005-01-01

    A retrospective epidemiological study (n = 7,875) of neurologically expressed disorders (NED) in ruminants before the onset of the bovine spongiform encephalopathy epidemic (years studied, 1980 to 1997) was carried out in Belgium. The archives of all veterinary laboratories and rabies and transmissible spongiform encephalopathy (TSE) epidemiosurveillance networks were consulted. For all species, a significantly higher number of NED with virological causes (rabies) was reported south of the Sambre-Meuse Valley. During the period 1992 to 1997, for which the data were complete, (i) the predicted annual incidence of NED varied significantly as a function of species and area (higher numbers in areas where rabies was present) but was always above 100 cases per million, and (ii) the mean incidence of suspected TSE cases and, among them, those investigated by histopathological examination varied significantly as a function of species and area. The positive predictive value of a presumptive clinical diagnosis of NED ranged from 0.13 (game) to 0.63 (sheep). Knowledge of the positive predictive value permits the definition of a reference point before certain actions (e.g., awareness and training campaigns) are undertaken. It also shows the usefulness of a systematic necropsy or complementary laboratory tests to establish an etiological diagnosis. TSE analysis of a small, targeted historical sampling (n = 48) permitted the confirmation of one case and uncovered another case of scrapie. The results of the present study help to develop and maintain the quality of the worldwide clinical epidemiological networks for TSE, especially in countries that in the past imported live animals, animal products, and feedstuffs from countries with TSE cases. PMID:15695693

  5. Evaluation of a closed loop inductive power transmission system on an awake behaving animal subject.

    PubMed

    Kiani, Mehdi; Kwon, Ki Yong; Zhang, Fei; Oweiss, Karim; Ghovanloo, Maysam

    2011-01-01

    This paper presents in vivo experimental results for a closed loop wireless power transmission system to implantable devices on an awake behaving animal subject. In this system, wireless power transmission takes place across an inductive link, controlled by a commercial off-the-shelf (COTS) radio frequency identification (RFID) transceiver (TRF7960) operating at 13.56 MHz. Induced voltage on the implantable secondary coil is rectified, digitized by a 10-bit analog to digital converter, and transmitted back to the primary via back telemetry. Transmitter (Tx) and receiver (Rx) circuitry were mounted on the back of an adult rat with a nominal distance of ~7 mm between their coils. Our experiments showed that the closed loop system was able to maintain the Rx supply voltage at the designated 3.8 V despite changes in the coils' relative distance and alignment due to animal movements. The Tx power consumption changed between 410 ~ 560 mW in order to deliver 27 mW to the receiver. The open loop system, on the other hand, showed undesired changes in the Rx supply voltage while the Tx power consumption was constant at 660 mW. PMID:22256112

  6. Retinal Fluorescence Spectroscopy for Diagnosis of Transmissible Spongiform Encephalopathies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Central nervous system (CNS) tissue provides optical signatures that can be detected with great sensitivity. The fundamental hypothesis proposed in this study was that diseased or damaged central nervous system (CNS) tissue produces optical signals that can be detected and made useful for diagnosti...

  7. Assessing the Susceptibility of Transgenic Mice Overexpressing Deer Prion Protein to Bovine Spongiform Encephalopathy

    PubMed Central

    Vickery, Christopher M.; Lockey, Richard; Holder, Thomas M.; Thorne, Leigh; Beck, Katy E.; Wilson, Christina; Denyer, Margaret; Sheehan, John; Marsh, Sarah; Webb, Paul R.; Dexter, Ian; Norman, Angela; Popescu, Emma; Schneider, Amanda; Holden, Paul; Griffiths, Peter C.; Plater, Jane M.; Dagleish, Mark P.; Martin, Stuart; Telling, Glenn C.; Simmons, Marion M.

    2014-01-01

    Several transgenic mouse models have been developed which facilitate the transmission of chronic wasting disease (CWD) of cervids and allow prion strain discrimination. The present study was designed to assess the susceptibility of the prototypic mouse line, Tg(CerPrP)1536+/−, to bovine spongiform encephalopathy (BSE) prions, which have the ability to overcome species barriers. Tg(CerPrP)1536+/− mice challenged with red deer-adapted BSE resulted in 90% to 100% attack rates, and BSE from cattle failed to transmit, indicating agent adaptation in the deer. PMID:24257620

  8. Bovine spongiform encephalopathy induces misfolding of alleged prion-resistant species cellular prion protein without altering its pathobiological features.

    PubMed

    Vidal, Enric; Fernández-Borges, Natalia; Pintado, Belén; Ordóñez, Montserrat; Márquez, Mercedes; Fondevila, Dolors; Torres, Juan María; Pumarola, Martí; Castilla, Joaquín

    2013-05-01

    Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, certain species closely related to humans, such as canids and leporids, were apparently resistant to BSE. In vitro prion amplification techniques (saPMCA) were used to successfully misfold the cellular prion protein (PrP(c)) of these allegedly resistant species into a BSE-type prion protein. The biochemical and biological properties of the new prions generated in vitro after seeding rabbit and dog brain homogenates with classical BSE were studied. Pathobiological features of the resultant prion strains were determined after their inoculation into transgenic mice expressing bovine and human PrP(C). Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE. This study provides a sound basis for risk assessment regarding prion diseases in purportedly resistant species. PMID:23637170

  9. Estimating the Relative Role of Various Subcategories of Food, Water, and Animal Contact Transmission of 28 Enteric Diseases in Canada

    PubMed Central

    Butler, Ainslie J.; Thomas, M. Kate

    2016-01-01

    Abstract Objective: Enteric illness represents a significant burden of illness in Canada and internationally. Building on previous research, an expert elicitation was undertaken to explore the routes of transmission for 28 pathogens involved in enteric illness in Canada. This article considers the subcategories of foodborne, waterborne, and animal contact transmission. Methods: As part of an expert elicitation, 31 experts were asked to provide estimates of source attribution for subcategories of foodborne (n = 15), waterborne (n = 10), and animal contact (n = 3) transmission. The results from an online survey were combined using triangular probability distributions, and median and 90% credible intervals were produced. The total proportion and estimated number of cases of enteric illness attributable to each type of food commodity, water source, and animal exposure route were calculated using results from the larger elicitation survey and from a recent Canadian foodborne burden of illness study (Thomas et al., 2013). Results: Thirty experts provided foodborne subcategory estimates for 15/28 pathogens, waterborne subcategory estimates for 14/28 pathogens and animal contact subcategory estimates for 5/28. The elicitation identified raw produce, recreational water, and farm animal contact as important risk factors for enteric illness. These results also highlighted the complexity of transmission, with greater uncertainty for certain pathogens and routes of transmission. Conclusions: This study is the first of its kind to explore subcategories of foodborne, waterborne, and animal contact transmission across such a range of enteric pathogens. Despite inherent uncertainty, these estimates present an important quantitative synthesis of the roles of foodborne commodities, water sources, and pathways of animal contact in the transmission of enteric illness in Canada. PMID:26863428

  10. Transmission of scrapie prions to primate after an extended silent incubation period

    PubMed Central

    Comoy, Emmanuel E.; Mikol, Jacqueline; Luccantoni-Freire, Sophie; Correia, Evelyne; Lescoutra-Etchegaray, Nathalie; Durand, Valérie; Dehen, Capucine; Andreoletti, Olivier; Casalone, Cristina; Richt, Juergen A.; Greenlee, Justin J.; Baron, Thierry; Benestad, Sylvie L.; Brown, Paul; Deslys, Jean-Philippe

    2015-01-01

    Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie. PMID:26123044

  11. Transmission of scrapie prions to primate after an extended silent incubation period.

    PubMed

    Comoy, Emmanuel E; Mikol, Jacqueline; Luccantoni-Freire, Sophie; Correia, Evelyne; Lescoutra-Etchegaray, Nathalie; Durand, Valérie; Dehen, Capucine; Andreoletti, Olivier; Casalone, Cristina; Richt, Juergen A; Greenlee, Justin J; Baron, Thierry; Benestad, Sylvie L; Brown, Paul; Deslys, Jean-Philippe

    2015-01-01

    Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie. PMID:26123044

  12. Vertical transmission and fetal damage in animal models of congenital toxoplasmosis: A systematic review.

    PubMed

    Vargas-Villavicencio, José Antonio; Besné-Mérida, Alejandro; Correa, Dolores

    2016-06-15

    In humans, the probability of congenital infection and fetal damage due to Toxoplasma gondii is dependent on the gestation period at which primary infection occurs. Many animal models have been used for vaccine, drug testing, or studies on host or parasite factors that affect transmission or fetal pathology, but few works have directly tested fetal infection and damage rates along gestation. So, the purpose of this work was to perform a systematic review of the literature to determine if there is a model which reflects these changes as they occur in humans. We looked for papers appearing between 1970 and 2014 in major databases like Medline and Scopus, as well as gray literature. From almost 11,000 citations obtained, only 49 papers fulfilled the criteria of having data of all independent variables and at least one dependent datum for control (untreated) groups. Some interesting findings could be extracted. For example, pigs seem resistant and sheep susceptible to congenital infection. Also, oocysts cause more congenitally infected offspring than tissue cysts, bradyzoites or tachyzoites. In spite of these interesting findings, very few results on vertical transmission or fetal damage rates were similar to those described for humans and only for one of the gestation thirds, not all. Moreover, in most designs tissue cysts - with unknown number of bradyzoites - were used, so actual dose could not be established. The meta-analysis could not be performed, mainly because of great heterogeneity in experimental conditions. Nevertheless, results gathered suggest that a model could be designed to represent the increase in vertical transmission and decrease in fetal damage found in humans under natural conditions. PMID:27198800

  13. Concise review: transmissible animal tumors as models of the cancer stem-cell process.

    PubMed

    O'Neill, Iain D

    2011-12-01

    Tasmanian devil facial tumor disease (DFTD) and canine transmissible venereal tumor (CTVT) are highly unusual cancers capable of being transmitted between animals as an allograft. The concept that these tumors represent a cancer stem-cell process has never been formally evaluated. For each, evidence of self-renewal is found in the natural history of these tumors in the wild, tumor initiation in recipient animals, and serial transplantation studies. Additional data for stem-cell-specific genes and markers in DFTD also exist. Although both tumor types manifest as undifferentiated cancers, immunocytohistochemistry supports a histiocytic phenotype for CTVT and a neural crest origin, possibly a Schwann-cell phenotype, for DFTD. In these data, differential expression of lineage markers is seen which may suggest some capacity for differentiation toward a heterogeneous variety of cell types. It is proposed that DFTD and CTVT may represent and may serve as models of the cancer stem-cell process, but formal investigation is required to clarify this. Appreciation of any such role may act as a stimulus to ongoing research in the pathology of DFTD and CTVT, including further characterization of their origin and phenotype and possible therapeutic approaches. Additionally, they may provide valuable models for future studies of their analogous human cancers, including any putative CSC component. PMID:21956952

  14. Does the Presence of Scrapie Affect the Ability of Current Statutory Discriminatory Tests To Detect the Presence of Bovine Spongiform Encephalopathy?

    PubMed

    Simmons, M M; Chaplin, M J; Vickery, C M; Simon, S; Davis, L; Denyer, M; Lockey, R; Stack, M J; O'Connor, M J; Bishop, K; Gough, K C; Maddison, B C; Thorne, L; Spiropoulos, J

    2015-08-01

    Current European Commission (EC) surveillance regulations require discriminatory testing of all transmissible spongiform encephalopathy (TSE)-positive small ruminant (SR) samples in order to classify them as bovine spongiform encephalopathy (BSE) or non-BSE. This requires a range of tests, including characterization by bioassay in mouse models. Since 2005, naturally occurring BSE has been identified in two goats. It has also been demonstrated that more than one distinct TSE strain can coinfect a single animal in natural field situations. This study assesses the ability of the statutory methods as listed in the regulation to identify BSE in a blinded series of brain samples, in which ovine BSE and distinct isolates of scrapie are mixed at various ratios ranging from 99% to 1%. Additionally, these current statutory tests were compared with a new in vitro discriminatory method, which uses serial protein misfolding cyclic amplification (sPMCA). Western blotting consistently detected 50% BSE within a mixture, but at higher dilutions it had variable success. The enzyme-linked immunosorbent assay (ELISA) method consistently detected BSE only when it was present as 99% of the mixture, with variable success at higher dilutions. Bioassay and sPMCA reported BSE in all samples where it was present, down to 1%. sPMCA also consistently detected the presence of BSE in mixtures at 0.1%. While bioassay is the only validated method that allows comprehensive phenotypic characterization of an unknown TSE isolate, the sPMCA assay appears to offer a fast and cost-effective alternative for the screening of unknown isolates when the purpose of the investigation was solely to determine the presence or absence of BSE. PMID:26041899

  15. Phenotype Shift from Atypical Scrapie to CH1641 following Experimental Transmission in Sheep

    PubMed Central

    Simmons, Marion M.; Moore, S. Jo; Lockey, Richard; Chaplin, Melanie J; Konold, Timm; Vickery, Christopher; Spiropoulos, John

    2015-01-01

    The interactions of host and infecting strain in ovine transmissible spongiform encephalopathies are known to be complex, and have a profound effect on the resulting phenotype of disease. In contrast to classical scrapie, the pathology in naturally-occurring cases of atypical scrapie appears more consistent, regardless of genotype, and is preserved on transmission within sheep homologous for the prion protein (PRNP) gene. However, the stability of transmissible spongiform encephalopathy phenotypes on passage across and within species is not absolute, and there are reports in the literature where experimental transmissions of particular isolates have resulted in a phenotype consistent with a different strain. In this study, intracerebral inoculation of atypical scrapie between two genotypes both associated with susceptibility to atypical forms of disease resulted in one sheep displaying an altered phenotype with clinical, pathological, biochemical and murine bioassay characteristics all consistent with the classical scrapie strain CH1641, and distinct from the atypical scrapie donor, while the second sheep did not succumb to challenge. One of two sheep orally challenged with the same inoculum developed atypical scrapie indistinguishable from the donor. This study adds to the range of transmissible spongiform encephalopathy phenotype changes that have been reported following various different experimental donor-recipient combinations. While these circumstances may not arise through natural exposure to disease in the field, there is the potential for iatrogenic exposure should current disease surveillance and feed controls be relaxed. Future sheep to sheep transmission of atypical scrapie might lead to instances of disease with an alternative phenotype and onward transmission potential which may have adverse implications for both public health and animal disease control policies. PMID:25710519

  16. Epidemiological and Genetic Data Supporting the Transmission of Ancylostoma ceylanicum among Human and Domestic Animals

    PubMed Central

    Ngui, Romano; Lim, Yvonne A. L.; Traub, Rebecca; Mahmud, Rohela; Mistam, Mohd Sani

    2012-01-01

    Background Currently, information on species-specific hookworm infection is unavailable in Malaysia and is restricted worldwide due to limited application of molecular diagnostic tools. Given the importance of accurate identification of hookworms, this study was conducted as part of an ongoing molecular epidemiological investigation aimed at providing the first documented data on species-specific hookworm infection, associated risk factors and the role of domestic animals as reservoirs for hookworm infections in endemic communities of Malaysia. Methods/Findings A total of 634 human and 105 domestic canine and feline fecal samples were randomly collected. The overall prevalence of hookworm in humans and animals determined via microscopy was 9.1% (95% CI = 7.0–11.7%) and 61.9% (95% CI = 51.2–71.2%), respectively. Multivariate analysis indicated that participants without the provision of proper latrine systems (OR = 3.5; 95% CI = 1.53–8.00; p = 0.003), walking barefooted (OR = 5.6; 95% CI = 2.91–10.73; p<0.001) and in close contact with pets or livestock (OR = 2.9; 95% CI = 1.19–7.15; p = 0.009) were more likely to be infected with hookworms. Molecular analysis revealed that while most hookworm-positive individuals were infected with Necator americanus, Ancylostoma ceylanicum constituted 12.8% of single infections and 10.6% mixed infections with N. americanus. As for cats and dogs, 52.0% were positive for A. ceylanicum, 46.0% for Ancylostoma caninum and 2.0% for Ancylostoma braziliense and all were single infections. Conclusion This present study provided evidence based on the combination of epidemiological, conventional diagnostic and molecular tools that A. ceylanicum infection is common and that its transmission dynamic in endemic areas in Malaysia is heightened by the close contact of human and domestic animal (i.e., dogs and cats) populations. PMID:22347515

  17. Sociality and health: impacts of sociality on disease susceptibility and transmission in animal and human societies

    PubMed Central

    Kappeler, Peter M.; Cremer, Sylvia; Nunn, Charles L.

    2015-01-01

    This paper introduces a theme issue presenting the latest developments in research on the impacts of sociality on health and fitness. The articles that follow cover research on societies ranging from insects to humans. Variation in measures of fitness (i.e. survival and reproduction) has been linked to various aspects of sociality in humans and animals alike, and variability in individual health and condition has been recognized as a key mediator of these relationships. Viewed from a broad evolutionary perspective, the evolutionary transitions from a solitary lifestyle to group living have resulted in several new health-related costs and benefits of sociality. Social transmission of parasites within groups represents a major cost of group living, but some behavioural mechanisms, such as grooming, have evolved repeatedly to reduce this cost. Group living also has created novel costs in terms of altered susceptibility to infectious and non-infectious disease as a result of the unavoidable physiological consequences of social competition and integration, which are partly alleviated by social buffering in some vertebrates. Here, we define the relevant aspects of sociality, summarize their health-related costs and benefits, and discuss possible fitness measures in different study systems. Given the pervasive effects of social factors on health and fitness, we propose a synthesis of existing conceptual approaches in disease ecology, ecological immunology and behavioural neurosciences by adding sociality as a key factor, with the goal to generate a broader framework for organismal integration of health-related research. PMID:25870402

  18. Reverse Zoonotic Disease Transmission (Zooanthroponosis): A Systematic Review of Seldom-Documented Human Biological Threats to Animals

    PubMed Central

    Messenger, Ali M.; Barnes, Amber N.; Gray, Gregory C.

    2014-01-01

    Background Research regarding zoonotic diseases often focuses on infectious diseases animals have given to humans. However, an increasing number of reports indicate that humans are transmitting pathogens to animals. Recent examples include methicillin-resistant Staphylococcus aureus, influenza A virus, Cryptosporidium parvum, and Ascaris lumbricoides. The aim of this review was to provide an overview of published literature regarding reverse zoonoses and highlight the need for future work in this area. Methods An initial broad literature review yielded 4763 titles, of which 4704 were excluded as not meeting inclusion criteria. After careful screening, 56 articles (from 56 countries over three decades) with documented human-to-animal disease transmission were included in this report. Findings In these publications, 21 (38%) pathogens studied were bacterial, 16 (29%) were viral, 12 (21%) were parasitic, and 7 (13%) were fungal, other, or involved multiple pathogens. Effected animals included wildlife (n = 28, 50%), livestock (n = 24, 43%), companion animals (n = 13, 23%), and various other animals or animals not explicitly mentioned (n = 2, 4%). Published reports of reverse zoonoses transmission occurred in every continent except Antarctica therefore indicating a worldwide disease threat. Interpretation As we see a global increase in industrial animal production, the rapid movement of humans and animals, and the habitats of humans and wild animals intertwining with great complexity, the future promises more opportunities for humans to cause reverse zoonoses. Scientific research must be conducted in this area to provide a richer understanding of emerging and reemerging disease threats. As a result, multidisciplinary approaches such as One Health will be needed to mitigate these problems. PMID:24586500

  19. [Epidemics of bovine spongiform encephalopathy and new variant of Creutzfeldt-Jakob disease in humans. Most recent findings on prion disease].

    PubMed

    Calza, L; Manfredi, R; Chiodo, F

    2001-02-01

    Prion diseases have been popularized by extensive media coverage of bovine spongiform encephalopathy (BSE) or "mad cow disease" epidemic, observed in Great Britain since 1986, and new variant Creutzfeldt-Jakob disease (nvCJD), reported for the first time in 1996. In contrast to the classical form of the disease, nvCJD affects younger patients, presents a relatively longer duration of illness and is caused by the same agent as BSE. Evidence from laboratory studies now strongly supports the hypothesis that new variant represents human form of animal disease, linked to exposure, probably through food, to bovine prions. Number of BSE reports in the United Kingdom began to decline in 1993, and has continuously decreased year by year since then, but a great worry spread in European countries in association with new BSE reported cases outside of the Great Britain, and increasing incidence of nvCJD. New epidemiological, clinical, histopathological and experimental data on prion diseases are reviewed, focusing our attention on the possible transmission of prion proteins from animals to humans. PMID:11294108

  20. Prion and prion-like diseases in animals.

    PubMed

    Aguilar-Calvo, Patricia; García, Consolación; Espinosa, Juan Carlos; Andreoletti, Olivier; Torres, Juan María

    2015-09-01

    Transmissible spongiform encephalopaties (TSEs) are fatal neurodegenerative diseases characterized by the aggregation and accumulation of the misfolded prion protein in the brain. Other proteins such as β-amyloid, tau or Serum Amyloid-A (SAA) seem to share with prions some aspects of their pathogenic mechanism; causing a variety of so called prion-like diseases in humans and/or animals such as Alzheimer's, Parkinson's, Huntington's, Type II diabetes mellitus or amyloidosis. The question remains whether these misfolding proteins have the ability to self-propagate and transmit in a similar manner to prions. In this review, we describe the prion and prion-like diseases affecting animals as well as the recent findings suggesting the prion-like transmissibility of certain non-prion proteins. PMID:25444937

  1. Bovine spongiform encephalopathy in Sweden: an H-type variant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE) had never been detected in Sweden until 2006, when the active surveillance identified a case in a 12-year-old cow. The case was an unusual form since several molecular features of the protease-resistant prion protein (PrP**res) were different from classical BSE...

  2. Generation of a Persistently Infected MDBK Cell Line with Natural Bovine Spongiform Encephalopathy (BSE)

    PubMed Central

    Tark, Dongseob; Kim, Hyojin; Neale, Michael H.; Kim, Minjeong; Sohn, Hyunjoo; Lee, Yoonhee; Cho, Insoo; Joo, Yiseok; Windl, Otto

    2015-01-01

    Bovine spongiform encephalopathy (BSE) is a zoonotic transmissible spongiform encephalopathy (TSE) thought to be caused by the same prion strain as variant Creutzfeldt-Jakob disease (vCJD). Unlike scrapie and chronic wasting disease there is no cell culture model allowing the replication of proteinase K resistant BSE (PrPBSE) and the further in vitro study of this disease. We have generated a cell line based on the Madin-Darby Bovine Kidney (MDBK) cell line over-expressing the bovine prion protein. After exposure to naturally BSE-infected bovine brain homogenate this cell line has shown to replicate and accumulate PrPBSE and maintain infection up to passage 83 after initial challenge. Collectively, we demonstrate, for the first time, that the BSE agent can infect cell lines over-expressing the bovine prion protein similar to other prion diseases. These BSE infected cells will provide a useful tool to facilitate the study of potential therapeutic agents and the diagnosis of BSE. PMID:25647616

  3. Prion Diseases as Transmissible Zoonotic Diseases

    PubMed Central

    Lee, Jeongmin; Kim, Su Yeon; Hwang, Kyu Jam; Ju, Young Ran; Woo, Hee-Jong

    2013-01-01

    Prion diseases, also called transmissible spongiform encephalopathies (TSEs), lead to neurological dysfunction in animals and are fatal. Infectious prion proteins are causative agents of many mammalian TSEs, including scrapie (in sheep), chronic wasting disease (in deer and elk), bovine spongiform encephalopathy (BSE; in cattle), and Creutzfeldt–Jakob disease (CJD; in humans). BSE, better known as mad cow disease, is among the many recently discovered zoonotic diseases. BSE cases were first reported in the United Kingdom in 1986. Variant CJD (vCJD) is a disease that was first detected in 1996, which affects humans and is linked to the BSE epidemic in cattle. vCJD is presumed to be caused by consumption of contaminated meat and other food products derived from affected cattle. The BSE epidemic peaked in 1992 and decreased thereafter; this decline is continuing sharply owing to intensive surveillance and screening programs in the Western world. However, there are still new outbreaks and/or progression of prion diseases, including atypical BSE, and iatrogenic CJD and vCJD via organ transplantation and blood transfusion. This paper summarizes studies on prions, particularly on prion molecular mechanisms, BSE, vCJD, and diagnostic procedures. Risk perception and communication policies of the European Union for the prevention of prion diseases are also addressed to provide recommendations for appropriate government policies in Korea. PMID:24159531

  4. Prion diseases as transmissible zoonotic diseases.

    PubMed

    Lee, Jeongmin; Kim, Su Yeon; Hwang, Kyu Jam; Ju, Young Ran; Woo, Hee-Jong

    2013-02-01

    Prion diseases, also called transmissible spongiform encephalopathies (TSEs), lead to neurological dysfunction in animals and are fatal. Infectious prion proteins are causative agents of many mammalian TSEs, including scrapie (in sheep), chronic wasting disease (in deer and elk), bovine spongiform encephalopathy (BSE; in cattle), and Creutzfeldt-Jakob disease (CJD; in humans). BSE, better known as mad cow disease, is among the many recently discovered zoonotic diseases. BSE cases were first reported in the United Kingdom in 1986. Variant CJD (vCJD) is a disease that was first detected in 1996, which affects humans and is linked to the BSE epidemic in cattle. vCJD is presumed to be caused by consumption of contaminated meat and other food products derived from affected cattle. The BSE epidemic peaked in 1992 and decreased thereafter; this decline is continuing sharply owing to intensive surveillance and screening programs in the Western world. However, there are still new outbreaks and/or progression of prion diseases, including atypical BSE, and iatrogenic CJD and vCJD via organ transplantation and blood transfusion. This paper summarizes studies on prions, particularly on prion molecular mechanisms, BSE, vCJD, and diagnostic procedures. Risk perception and communication policies of the European Union for the prevention of prion diseases are also addressed to provide recommendations for appropriate government policies in Korea. PMID:24159531

  5. Transmission and dose–response experiments for social animals: a reappraisal of the colonization biology of Campylobacter jejuni in chickens

    PubMed Central

    Conlan, Andrew J. K.; Line, John E.; Hiett, Kelli; Coward, Chris; Van Diemen, Pauline M.; Stevens, Mark P.; Jones, Michael A.; Gog, Julia R.; Maskell, Duncan J.

    2011-01-01

    Dose–response experiments characterize the relationship between infectious agents and their hosts. These experiments are routinely used to estimate the minimum effective infectious dose for an infectious agent, which is most commonly characterized by the dose at which 50 per cent of challenged hosts become infected—the ID50. In turn, the ID50 is often used to compare between different agents and quantify the effect of treatment regimes. The statistical analysis of dose–response data typically makes the assumption that hosts within a given dose group are independent. For social animals, in particular avian species, hosts are routinely housed together in groups during experimental studies. For experiments with non-infectious agents, this poses no practical or theoretical problems. However, transmission of infectious agents between co-housed animals will modify the observed dose–response relationship with implications for the estimation of the ID50 and the comparison between different agents and treatments. We derive a simple correction to the likelihood for standard dose–response models that allows us to estimate dose–response and transmission parameters simultaneously. We use this model to show that: transmission between co-housed animals reduces the apparent value of the ID50 and increases the variability between replicates leading to a distinctive all-or-nothing response; in terms of the total number of animals used, individual housing is always the most efficient experimental design for ascertaining dose–response relationships; estimates of transmission from previously published experimental data for Campylobacter spp. in chickens suggest that considerable transmission occurred, greatly increasing the uncertainty in the estimates of dose–response parameters reported in the literature. Furthermore, we demonstrate that accounting for transmission in the analysis of dose–response data for Campylobacter spp. challenges our current understanding of

  6. Transmissible amyloid.

    PubMed

    Tjernberg, L O; Rising, A; Johansson, J; Jaudzems, K; Westermark, P

    2016-08-01

    There are around 30 human diseases associated with protein misfolding and amyloid formation, each one caused by a certain protein or peptide. Many of these diseases are lethal and together they pose an enormous burden to society. The prion protein has attracted particular interest as being shown to be the pathogenic agent in transmissible diseases such as kuru, Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Whether similar transmission could occur also in other amyloidoses such as Alzheimer's disease, Parkinson's disease and serum amyloid A amyloidosis is a matter of intense research and debate. Furthermore, it has been suggested that novel biomaterials such as artificial spider silk are potentially amyloidogenic. Here, we provide a brief introduction to amyloid, prions and other proteins involved in amyloid disease and review recent evidence for their potential transmission. We discuss the similarities and differences between amyloid and silk, as well as the potential hazards associated with protein-based biomaterials. PMID:27002185

  7. Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: background, evolution, and current concerns.

    PubMed Central

    Brown, P.; Will, R. G.; Bradley, R.; Asher, D. M.; Detwiler, L.

    2001-01-01

    The epidemic of bovine spongiform encephalopathy (BSE) in the United Kingdom, which began in 1986 and has affected nearly 200,000 cattle, is waning to a conclusion, but leaves in its wake an outbreak of human Creutzfeldt-Jakob disease, most probably resulting from the consumption of beef products contaminated by central nervous system tissue. Although averaging only 10-15 cases a year since its first appearance in 1994, its future magnitude and geographic distribution (in countries that have imported infected British cattle or cattle products, or have endogenous BSE) cannot yet be predicted. The possibility that large numbers of apparently healthy persons might be incubating the disease raises concerns about iatrogenic transmissions through instrumentation (surgery and medical diagnostic procedures) and blood and organ donations. Government agencies in many countries continue to implement new measures to minimize this risk. PMID:11266289

  8. Endoscopic ultrasound-guided inoculation of transmissible venereal tumor in the colon: A large animal model for colon neoplasia

    PubMed Central

    Bhutani, Manoop S.; Uthamanthil, Rajesh; Suzuki, Rei; Shetty, Anil; Klumpp, Sherry A.; Nau, William; Stafford, Roger Jason

    2016-01-01

    Background: To develop and evaluate the feasibility of emerging interventions, animal models with accurate anatomical environment are required. Objectives: We aimed to establish a clinically relevant colorectal tumor model with canine transmissible venereal tumor (CTVT) utilizing endoscopic ultrasound (EUS) imaging guidance. Design: Survival study using a canine model. Setting: Endoscopic animal research laboratory at a tertiary cancer center. Materials and Methods: This study involved five canines. Interventions: A colorectal tumor model was established and evaluated in five canines under cyclosporine immune suppression. Under endoscopic imaging guidance, saline was injected into the submucosal layer forming a bleb. Subsequently, CTVT was inoculated into the bleb under EUS guidance. Endoscopy was the primary method of assessing tumor growth. Tumors developed in 60-130 days. Upon detection of lesions >1 cm, the animals were euthanized and the tumors were harvested for histopathological characterization. Main outcome measurements: Success rate of tumor growth. The presence or absence of vasculature inside tumors. Results: Colorectal tumor successfully developed in three out of the five animals (60%). Among the ones with tumor growth, average inoculated CTVT volume, incubation time, and tumor size was 1.8 cc, 65.7 days, and 2.0 cm, respectively. The two animals without tumor growth were observed for >100 days. In all the tumors, vascular structure was characterized with CD31 imunohistochemical stain. Limitations: Small number of animals. Conclusion: We succeeded in creating a new colorectal tumor canine model with CTVT utilizing EUS. PMID:27080606

  9. Reducing foodborne pathogen persistence and transmission in animal production environments: Challenges and Opportunities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Preharvest strategies to reduce zoonotic pathogens in food animals are important components of the farm-to-table food safety continuum. The problem is complex; there are multiple pathogens of concern, multiple animal species under different production and management systems, and a variety of source...

  10. Detection of ruminant meat and bone meals in animal feed by real-time polymerase chain reaction: result of an interlaboratory study.

    PubMed

    Prado, Marta; Berben, Gilbert; Fumière, Olivier; van Duijn, Gert; Mensinga-Kruize, Jonne; Reaney, Scott; Boix, Ana; von Holst, Christoph

    2007-09-01

    The commercialization of animal feeds infected by prions proved to be the main cause of transmission of bovine spongiform encephalopathy (BSE). Therefore, feed bans were enforced, initially for ruminant feeds, and later for all feeds for farmed animals. The development and validation of analytical methods for the species-specific detection of animal proteins in animal feed has been indicated in the TSE (Transmissible Spongiform Encephalopathies) Roadmap (European Commission. The TSE (Transmissible Spongiform Encephalopathy) roadmap. URL: http://europa.eu.int/comm/food/food/biosafety/bse/roadmap_en.pdf, 2005) as the main condition for lifting the extended feed ban. Methods based on polymerase chain reaction (PCR) seem to be a promising solution for this aim. The main objective of this study was to determine the applicability of four different real-time PCR methods, developed by three National expert laboratories from the European Union (EU), for the detection and identification of cattle or ruminant species in typical compound feeds, fortified with meat and bone meals (MBM) from different animal species at different concentration levels. The MBM samples utilized in this study have been treated using the sterilization condition mandatory within the European Union (steam pressure sterilization at 133 degrees C, 3 bar, and 20 min), which is an additional challenge to the PCR methods evaluated in this study. The results indicate that the three labs applying their PCR methods were able to detect 0.1% of cattle MBM, either alone or in mixtures with different materials such as fishmeal, which demonstrates the improvement made by this technique, especially when compared with results from former interlaboratory studies. PMID:17725317

  11. Abnormal regulation of TSG101 in mice with spongiform neurodegeneration

    PubMed Central

    Jiao, Jian; Sun, Kaihua; Walker, Will P.; Bagher, Pooneh; Cota, Christina D.; Gunn, Teresa M.

    2009-01-01

    Summary Spongiform neurodegeneration is characterized by the appearance of vacuoles throughout the central nervous system. It has many potential causes, but the underlying cellular mechanisms are not well understood. Mice lacking the E3 ubiquitin ligase Mahogunin Ring Finger-1 (MGRN1) develop age-dependent spongiform encephalopathy. We identified an interaction between a “PSAP” motif in MGRN1 and the ubiquitin E2 variant (UEV) domain of TSG101, a component of the endosomal sorting complex required for transport I (ESCRT-I), and demonstrate that MGRN1 multimonoubiquitinates TSG101. We examined the in vivo consequences of loss of MGRN1 on TSG101 expression and function in the mouse brain. The pattern of TSG101 ubiquitination differed in the brains of wild-type mice and Mgrn1 null mutant mice: at 1 month of age, null mutant mice had less ubiquitinated TSG101, while in adults, mutant mice had more ubiquitinated, insoluble TSG101 than wild-type mice. There was an associated increase in epidermal growth factor receptor (EGFR) levels in mutant brains. These results suggest that loss of MGRN1 promotes ubiquitination of TSG101 by other E3s and may prevent its disassociation from endosomal membranes or cause it to form insoluble aggregates. Our data implicate loss of normal TSG101 function in endo-lysosomal trafficking in the pathogenesis of spongiform neurodegeneration in Mgrn1 null mutant mice. PMID:19703557

  12. Monte Carlo modelling of singles-mode transmission data for small animal PET scanners

    NASA Astrophysics Data System (ADS)

    Vandervoort, Eric; Camborde, Marie-Laure; Jan, Sébastien; Sossi, Vesna

    2007-06-01

    The attenuation corrections factors (ACFs), which are necessary for quantitatively accurate PET imaging, can be obtained using singles-mode transmission scanning. However, contamination from scatter is a largely unresolved problem for these data. We present an extension of the Monte Carlo simulation tool, GATE, for singles-mode transmission data and its validation using experimental data from the microPET R4 and Focus 120 scanners. We first validated our simulated PET scanner for coincidence-mode data where we found that experimental resolution and scatter fractions (SFs) agreed well for simulations that included positron interactions and scatter in the source material. After modifying GATE to model singles-mode data, we compared simulated and experimental ACFs and SFs for three different sized water cylinders using 57Co (122 keV photon emitter) and 68Ge (positron emitter) transmission sources. We also propose a simple correction for a large background contamination we identified in the 68Ge singles-mode data due to intrinsic 176Lu radioactivity present in the detector crystals. For simulation data, the SFs agreed to within 1.5% and 2.5% of experimental values for background-corrected 68Ge and 57Co transmission data, respectively. This new simulation tool accurately models the photon interactions and data acquisition for singles-mode transmission scans.

  13. A novel spongiform degeneration of the grey matter in the brain of a kitten.

    PubMed

    Vidal, E; Montoliu, P; Añor, S; Sisó, S; Ferrer, I; Pumarola, M

    2004-07-01

    A young female domestic short-hair cat presented with neurological signs consistent with a multifocal encephalic lesion (depressed mental status, head tilt to the right, cervical ventroflexion, head tremors, tetraparesis, conscious propioceptive deficits in all four limbs and visual deficits). No gross lesions were seen at necropsy. On light microscopical examination lesions were found only in the brain and cervical spinal cord. A generalized vacuolation of the grey matter of the brain was observed. Special staining techniques, immunohistochemistry, lectin affinity histochemistry and ultrastructural studies were performed to characterize the lesion; preservation of the white matter and a reactive astrogliosis were demonstrated. Feline retroviruses and PrPsc were not detected. Ultrastructurally, a dilatation of intracytoplasmic membrane-bounded organelles with membrane disruption and dendritic and somatic swelling was found in astrocytes and neurons. The age of the animal and histological changes suggested a novel, possibly congenital, spongiform degeneration of the brain and cervical spinal cord. PMID:15144805

  14. Animator

    ERIC Educational Resources Information Center

    Tech Directions, 2008

    2008-01-01

    Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…

  15. Transmission of Sarcoptes scabiei from animal to man and its control.

    PubMed

    Mitra, M; Mahanta, S K; Sen, S; Ghosh, C; Hati, A K

    1995-04-01

    Outbreak of Sarcoptes scabiei in animals spilling over to man in close association was observed in two adjacent villages, Fewgram and Nurpur in the district of Birbhum, West Bengal, from mid-November to mid-December, 1991. Nineteen goats and one calf who did not receive any treatment died of sarcoptic manage. All infected animals got cured with external application of deltamethrin, a synthetic pyrethroid and triazapentadiene. Human cases were treated successfully with benzene hexachloride (2%). PMID:8699041

  16. Cross-species transmission of TSE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction Transmissible spongiform encephalopathy (TSE) agents or prions induce fatal neurodegenerative diseases in humans and in other mammalian species. They are transmissible among their species of origin, but they can also cross the species barrier and induce infection and/or disease in other...

  17. Progressive accumulation of the abnormal conformer of the prion protein and spongiform encephalopathy in the obex of nonsymptomatic and symptomatic Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic wasting disease (CWD), a transmissible spongiform encephalopathy, has been reported in captive and free-ranging cervids. An abnormal isoform of a prion protein (PrP-CWD) has been associated with CWD in Rocky Mountain elk (Cervus elaphus nelsoni) and this prion protein can be detected with i...

  18. [Identification of Animal Whole Blood Based on Near Infrared Transmission Spectroscopy].

    PubMed

    Wan, Xiong; Wang, Jian; Liu, Peng-xi; Zhang, Ting-ting

    2016-01-01

    The inspection and classification for blood products are important but complicated in import-export ports or inspection and quarantine departments. For the inspection of whole blood products, open sampling can cause pollution and virulence factors in bloods samples may even endanger inspectors. Thus non-contact classification and identification methods for whole bloods of animals are needed. Spectroscopic techniques adopted in the flowcytometry need sampling blood cells during the detection; therefore they can not meet the demand of non-contact identification and classification for whole bloods of animals. Infrared absorption spectroscopy is a technique that can be used to analyze the molecular structure and chemical bonds of detected samples under the condition of non-contact. To find a feasible spectroscopic approach of non-contact detection for the species variation in whole blood samples, a near infrared transmitted spectra (NITS, 4 497.669 - 7 506.4 cm(-1)) experiment of whole blood samples of three common animals including chickens, dogs and cats has been conducted. During the experiment, the spectroscopic resolution is 5 cm(-1), and each spectrogram is an average of 5 measured spectral data. Experimental results show that all samples have a sharp absorption peak between 5 184 and 5 215 cm(-1), and a gentle absorption peak near 7 000 cm(-1). Besides, the NITS curves of different samples of same animals are similar, and only have slight differences in the whole transmittance. A correlation coefficient (CC) is induced to distinguish the differences of the three animals' whole bloods in NITS curves, and the computed CCs between NITS curves of different samples of the same animals, are greater than 0.99, whereas CCs between NITS curves of the whole bloods of different animals are from 0.509 48 to 0.916 13. Among which CCs between NITS curves of the whole bloods of chickens and cats are from 0.857 23 to 0.912 44, CCs between NITS curves of the whole bloods of

  19. Selection for Simple Major Surface Protein 2 Variants during Anaplasma marginale Transmission to Immunologically Naive Animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Anaplasma marginale, a rickettsial pathogen, evades clearance in the animal host by antigenic variation. Under immune selection, A. marginale expresses complex MSP2 mosaics, derived from multiple donor sequences. However, these mosaics have a selective advantage only in the presence of adaptive immu...

  20. Risk of parasite transmission influences perceived vulnerability to disease and perceived danger of disease-relevant animals.

    PubMed

    Prokop, Pavol; Usak, Muhammet; Fancovicová, Jana

    2010-09-01

    Adaptationist view proposes that emotions were shaped by natural selection and their primary function is to protect humans against predators and/or disease threat. This study examined cross-cultural and inter-personal differences in behavioural immune system measured by disgust, fear and perceived danger in participants from high (Turkey) and low (Slovakia) pathogen prevalence areas. We found that behavioural immune system in Turkish participants was activated more than those of Slovakian participants when exposed to photographs depicting disease-relevant cues, but not when exposed to disease-irrelevant cues. However, participants from Slovakia, where human to human disease transmission is expected to be more prevalent than in Turkey, showed lower aversion in Germ Aversion subscale supporting hypersensitiveness of the behavioural immune system. Having animals at home was less frequent both in Turkey and in participants who perceived higher danger about disease relevant animals. Participants more vulnerable to diseases reported higher incidence of illness last year and considered perceived disease-relevant animals more dangerous than others. Females showed greater fear, disgust and danger about disease-relevant animals than males. Our results further support the finding that cultural and inter-personal differences in human personality are influenced by parasite threat. PMID:20558257

  1. Evaluation of the zoonotic potential of transmissible mink encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Successful transmission of Transmissible Mink Encephalopathy (TME) to cattle supports the bovine hypothesis to the still controversial origin of TME outbreaks. Human and primate susceptibility to classical Bovine Spongiform Encephalopathy (c-BSE) and the transmissibility of L-type BSE to macaques as...

  2. Experimental transmission of scrapie agent to susceptible sheep by intralingual and intracerebral inoculation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Scrapie, a transmissible spongiform encephalopathy (TSE), is a naturally occurring fatal neurodegenerative disease of sheep and goats. This study documents incubation periods, pathological findings and distribution of abnormal prion proteins (PrP**res) by immunohistochemistry in tissues of genetical...

  3. H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism: clinical and pathologic features in wild-type and E211K cattle following intracranial inoculation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2006 an H-type bovine spongiform encephalopathy (BSE) case was reported in an animal with an unusual polymorphism (E211K) in the prion protein gene. Although the prevalence of this polymorphism is low, cattle carrying the K211 allele are predisposed to rapid onset of H-type BSE when exposed. The ...

  4. A small animal PET based on GAPDs and charge signal transmission approach for hybrid PET-MR imaging

    NASA Astrophysics Data System (ADS)

    Kang, Jihoon; Choi, Yong; Hong, Key Jo; Hu, Wei; Jung, Jin Ho; Huh, Yoonsuk; Kim, Byung-Tae

    2011-08-01

    Positron emission tomography (PET) employing Geiger-mode avalanche photodiodes (GAPDs) and charge signal transmission approach was developed for small animal imaging. Animal PET contained 16 LYSO and GAPD detector modules that were arranged in a 70 mm diameter ring with an axial field of view of 13 mm. The GAPDs charge output signals were transmitted to a preamplifier located remotely using 300 cm flexible flat cables. The position decoder circuits (PDCs) were used to multiplex the PET signals from 256 to 4 channels. The outputs of the PDCs were digitized and further-processed in the data acquisition unit. The cross-compatibilities of the PET detectors and MRI were assessed outside and inside the MRI. Experimental studies of the developed full ring PET were performed to examine the spatial resolution and sensitivity. Phantom and mouse images were acquired to examine the imaging performance. The mean energy and time resolution of the PET detector were 17.6% and 1.5 ns, respectively. No obvious degradation on PET and MRI was observed during simultaneous PET-MRI data acquisition. The measured spatial resolution and sensitivity at the CFOV were 2.8 mm and 0.7%, respectively. In addition, a 3 mm diameter line source was clearly resolved in the hot-sphere phantom images. The reconstructed transaxial PET images of the mouse brain and tumor displaying the glucose metabolism patterns were imaged well. These results demonstrate GAPD and the charge signal transmission approach can allow the development of high performance small animal PET with improved MR compatibility.

  5. Dysregulation of AMPA receptor transmission in the nucleus accumbens in animal models of cocaine addiction

    PubMed Central

    Wolf, Marina E.

    2014-01-01

    Plasticity of glutamate transmission in neuronal circuits involving the nucleus accumbens (NAc) is now recognized to play a critical role in cocaine addiction. NAc neurons are excited primarily by AMPA-type glutamate receptors (AMPAR) and this is required for cocaine seeking. This review will briefly describe AMPAR properties and trafficking, with a focus on studies in NAc neurons, and then consider mechanisms by which cocaine may alter AMPAR transmission. Two examples will be discussed that may be important in two different stages of addiction: learning about drugs and drug-related cues during the period of drug exposure, and persistent vulnerability to craving and relapse after abstinence is achieved. The first example is drawn from studies of cultured NAc neurons. Elevation of DA levels (as would occur following cocaine exposure) facilitates activity-dependent strengthening of excitatory synapses onto medium spiny neurons, the main cell type and projection neuron of the NAc. This occurs because activation of D1-class receptors primes AMPAR for synaptic insertion, creating a temporal window in which stimuli related to cocaine-taking are more efficacious at eliciting synaptic plasticity and thus being encoded into memory. The second example involves rat models of cocaine addiction. Cell surface and synaptic expression of AMPAR on NAc neurons is persistently increased after withdrawal from repeated cocaine exposure. We hypothesize that this increases the reactivity of NAc neurons to glutamate inputs from cortex and limbic structures, facilitating the ability of these inputs to trigger cocaine seeking and thus contributing to the persistent vulnerability to relapse that characterizes addiction. PMID:20361291

  6. Evaluating the risk of pathogen transmission from wild animals to domestic pigs in Australia.

    PubMed

    Pearson, Hayley E; Toribio, Jenny-Ann L M L; Lapidge, Steven J; Hernández-Jover, Marta

    2016-01-01

    Wild animals contribute to endemic infection in livestock as well as the introduction, reintroduction and maintenance of pathogens. The source of introduction of endemic diseases to a piggery is often unknown and the extent of wildlife contribution to such local spread is largely unexplored. The aim of the current study was to quantitatively assess the probability of domestic pigs being exposed to different pathogens from wild animals commonly found around commercial piggeries in Australia. Specifically, this study aims to quantify the probability of exposure to the pathogens Escherichia coli, Salmonella spp. and Campylobacter spp. from European starlings (Sturnus vulgarus); Brachyspira hyodysenteriae, Lawsonia intracellularis and Salmonella spp. from rats (Rattus rattus and Rattus norvegicus); and Mycoplasma hyopneumoniae, Leptospira spp., Brucella suis and L. intracellularis from feral pigs (Sus scrofa). Exposure assessments, using scenario trees and Monte Carlo stochastic simulation modelling, were conducted to identify potential pathways of introduction and calculate the probabilities of these pathways occurring. Input parameters were estimated from a national postal survey of commercial pork producers and from disease detection studies conducted for European starlings, rats and feral pigs in close proximity to commercial piggeries in Australia. Based on the results of the exposure assessments, rats presented the highest probability of exposure of pathogens to domestic pigs at any point in time, and L. intracellularis (median 0.13, 5% and 95%, 0.05-0.23) and B. hyodysenteriae (median 0.10, 0.05-0.19) were the most likely pathogens to be transmitted. Regarding European starlings, the median probability of exposure of domestic pigs to pathogenic E. coli at any point in time was estimated to be 0.03 (0.02-0.04). The highest probability of domestic pig exposure to feral pig pathogens at any point in time was found to be for M. hyopneumoniae (median 0.013, 0

  7. Synaptic transmission changes in fear memory circuits underlie key features of an animal model of schizophrenia.

    PubMed

    Pollard, Marie; Varin, Christophe; Hrupka, Brian; Pemberton, Darrel J; Steckler, Thomas; Shaban, Hamdy

    2012-02-01

    Non-competitive antagonists of the N-methyl-d-aspartate receptor (NMDA) such as phencyclidine (PCP) elicit schizophrenia-like symptoms in healthy individuals. Similarly, PCP dosing in rats produces typical behavioral phenotypes that mimic human schizophrenia symptoms. Although schizophrenic behavioral phenotypes of the PCP model have been extensively studied, the underlying alterations of intrinsic neuronal properties and synaptic transmission in relevant limbic brain microcircuits remain elusive. Acute brain slice electrophysiology and immunostaining of inhibitory neurons were used to identify neuronal circuit alterations of the amygdala and hippocampus associated with changes in extinction of fear learning in rats following PCP treatment. Subchronic PCP application led to impaired long-term potentiation (LTP) and marked increases in the ratio of NMDA to 2-amino-3(5-methyl-3-oxo-1,2-oxazol-4-yl)propionic acid (AMPA) receptor-mediated currents at lateral amygdala (LA) principal neurons without alterations in parvalbumin (PV) as well as non-PV, glutamic acid decarboxylase 67 (GAD 67) immunopositive neurons. In addition, LTP was impaired at the Schaffer collateral to CA1 hippocampal pathway coincident with a reduction in colocalized PV and GAD67 immunopositive neurons in the CA3 hippocampal area. These effects occurred without changes in spontaneous events or intrinsic membrane properties of principal cells in the LA. The impairment of LTP at both amygdalar and hippocampal microcircuits, which play a key role in processing relevant survival information such as fear and extinction memory concurred with a disruption of extinction learning of fear conditioned responses. Our results show that subchronic PCP administration in rats impairs synaptic functioning in the amygdala and hippocampus as well as processing of fear-related memories. PMID:22085880

  8. Identification of a Highly Transmissible Animal-Independent Staphylococcus aureus ST398 Clone with Distinct Genomic and Cell Adhesion Properties

    PubMed Central

    Uhlemann, Anne-Catrin; Porcella, Stephen F.; Trivedi, Sheetal; Sullivan, Sean B.; Hafer, Cory; Kennedy, Adam D.; Barbian, Kent D.; McCarthy, Alex J.; Street, Craig; Hirschberg, David L.; Lipkin, W. Ian; Lindsay, Jodi A.; DeLeo, Frank R.; Lowy, Franklin D.

    2012-01-01

    ABSTRACT A methicillin-resistant Staphylococcus aureus (MRSA) clone known as ST398 has emerged as a major cause of acute infections in individuals who have close contact with livestock. More recently, the emergence of an animal-independent ST398 methicillin-sensitive S. aureus (MSSA) clone has been documented in several countries. However, the limited surveillance of MSSA has precluded an accurate assessment of the global spread of ST398 and its clinical relevance. Here we provide evidence that ST398 is a frequent source of MSSA infections in northern Manhattan and is readily transmitted between individuals in households. This contrasts with the limited transmissibility of livestock-associated ST398 (LA-ST398) MRSA strains between humans. Our whole-genome sequence analysis revealed that the chromosome of the human-associated ST398 MSSA clone is smaller than that of the LA-ST398 MRSA reference strain S0385, due mainly to fewer mobile genetic elements (MGEs). In contrast, human ST398 MSSA isolates harbored the prophage φ3 and the human-specific immune evasion cluster (IEC) genes chp and scn. While most of the core genome was conserved between the human ST398 MSSA clone and S0385, these strains differed substantially in their repertoire and composition of intact adhesion genes. These genetic changes were associated with significantly enhanced adhesion of human ST398 MSSA isolates to human skin keratinocytes and keratin. We propose that the human ST398 MSSA clone can spread independent of animal contact using an optimized repertoire of MGEs and adhesion molecules adapted to transmission among humans. PMID:22375071

  9. Potential for transmission of prion disease by contact lenses: an assessment of risk.

    PubMed

    Hogan, R Nick

    2003-01-01

    Prions are small proteinaceous infectious agents known to cause central nervous system infections in both animals and humans. Interest in the pathogenesis of these diseases has grown since the emergence of bovine spongiform encephalopathy (BSE or "mad cow disease") in the United Kingdom and several other countries in Europe. Ingestion of meat products from animals infected with BSE has resulted in transmission of the disease to humans as a variant form of Creutzfeldt-Jakob Disease (vCJD). CJD has a long asymptomatic incubation period, is untreatable, and universally fatal. Hence concern has arisen over other possible routes of disease transmission. Because it is known that prions are found in low levels in the corneas of animals with experimentally induced prion disease, and that a case of human CJD transmission by corneal transplantation has occurred, the question of possible prion transmission through the reuse of diagnostic fitting of contact lenses has surfaced. This article reviews prion diseases of animals and humans, and the data regarding the presence and location of prions in the eye. Issues inherent in the question of corneal and contact lens transmission are discussed. Although some key information has yet to be derived, it appears that the chance of obtaining prion disease through contact lens use is negligible. PMID:12772730

  10. [Clinical findings in 50 cows with bovine spongiform encephalopathy (BSE)].

    PubMed

    Braun, U; Schicker, E; Pusterla, N; Schönmann, M

    1998-01-01

    The goal of this study was to describe the clinical findings in 50 cows with bovine spongiform encephalopathy (BSE). The most important abnormalities were disturbances in behaviour, sensitivity and locomotion. Of 48 cows with behavioural abnormalities, 33 were panic-stricken, 33 were fearful and 32 were restless and nervous. Other behavioural disturbances included bruxism (n = 23), salivation (n = 15), licking of the muzzle (n = 15) and flehmen (n = 8). Hypersensitivity to touching of the head and neck with a pen and reacted by throwing the head sideways, head shaking, curling the muzzle or flehmen and salivating. Hypersensitivity to sound was observed in 41 cows. Hypersensitivity to light was seen in 22 cows. disturbances in locomotion occurred in 44 cows. In 41, there was ataxia, which was generalized in 28 and restricted to the hindend in 13. PMID:9499623

  11. Control and eradication of animal diseases in New Zealand.

    PubMed

    Davidson, R M

    2002-01-01

    New Zealand is free from all the major epidemic (Office International des Epizooties List A) diseases of animals and other important diseases, such as rabies and the transmissible spongiform encephalopathies. The once endemic conditions of sheep scab (Psoroptes ovis), bovine brucellosis (Brucella abortus), hydatids (Echinococcus granulosus) and Aujeszky's disease have been eradicated. Anthrax (Bacillus anthracis) is no longer considered endemic and Pullorum disease (Salmonella Pullorum) has effectively been eradicated from commercial poultry flocks. There are current control programmes for bovine tuberculosis (Mycobacterium bovis), enzootic bovine leucosis in dairy cattle, infectious bursal disease, ovine epididymitis (Brucella ovis), and caprine arthritis encephalitis. Historically, incursions by three important non-endemic diseases, contagious bovine pleuropneumonia, classical swine fever and scrapie, have been successfully eliminated. Any new occurrence of a serious exotic disease would be dealt with swiftly using powerful legislative authorities available for the purpose. PMID:16032229

  12. Co-Distribution of Aβ Plaques and Spongiform Degeneration in Familial Creutzfeldt - Jakob Disease with E200K-129M Haplotype

    PubMed Central

    Ghoshal, Nupur; Cali, Ignazio; Perrin, Richard Justin; Josephson, Scott Andrew; Sun, Ning; Gambetti, Pierluigi; Morris, John Carl

    2009-01-01

    BACKGROUND Dominantly inherited Creutzfeldt-Jakob disease (CJD) comprises 5–15% of all CJD cases. The E200K mutation in the prion protein (PrP) gene (PRNP) is the most frequent cause of familial CJD. Co-existent amyloid-beta (Aβ) pathology has been reported in some transmissible spongiform encephalopathies but not in familial CJD with the E200K mutation. OBJECTIVE To characterize a CJD family in which Aβ pathology co-distributes with spongiform degeneration. DESIGN Clinicopathological and molecular study of a family with CJD with the E200K-129M haplotype. SETTING Alzheimer’s disease research center MAIN OUTCOME MEASURES Clinical, biochemical, and neuropathological observations of 2 generations of a family. RESULTS In this kindred, three autopsied individuals showed pathological changes typical for this haplotype: spongiform degeneration, gliosis, neuronal loss, and PrP deposition. Moreover, two of these cases (ages 57 and 63) showed numerous Aβ plaques co-distributed with the spongiform degeneration. APOE genotyping in 2 cases revealed that Aβ plaques were present in the APOE4 carrier but not in the APOE4 noncarrier. Two additional individuals exhibited incomplete penetrance as they had no clinical evidence of CJD at death after age 80 and yet had affected siblings and children. CONCLUSION This is the first description of Aβ pathology in familial CJD with the E200K mutation. The co-distribution of plaques and CJD-associated changes suggests that PrP plays a central role in Aβ formation and that Aβ pathology and prion disease likely influence each other. The kindred described here provides support that PrPE200K may also result in increased Aβ deposition. PMID:19822779

  13. Social and Economic Aspects of the Transmission of Pathogenic Bacteria between Wildlife and Food Animals: A Thematic Analysis of Published Research Knowledge.

    PubMed

    Fournier, A; Young, I; Rajić, A; Greig, J; LeJeune, J

    2015-09-01

    Wildlife is a known reservoir of pathogenic bacteria, including Mycobacterium bovis and Brucella spp. Transmission of these pathogens between wildlife and food animals can lead to damaging impacts on the agri-food industry and public health. Several international case studies have highlighted the complex and cross-sectoral challenges involved in preventing and managing these potential transmission risks. The objective of our study was to develop a better understanding of the socio-economic aspects of the transmission of pathogenic bacteria between wildlife and food animals to support more effective and sustainable risk mitigation strategies. We conducted qualitative thematic analysis on a purposive sample of 30/141 articles identified in a complementary scoping review of the literature in this area and identified two key themes. The first related to the framing of this issue as a 'wicked problem' that depends on a complex interaction of social factors and risk perceptions, governance and public policy, and economic implications. The second theme consisted of promising approaches and strategies to prevent and mitigate the potential risks from transmission of pathogenic bacteria between wildlife and food animals. These included participatory, collaborative and multidisciplinary decision-making approaches and the proactive incorporation of credible scientific evidence and local contextual factors into solutions. The integration of these approaches to address 'wicked problems' in this field may assist stakeholders and decision-makers in improving the acceptability and sustainability of future strategies to reduce the transmission of pathogenic bacteria between wildlife and food animals. PMID:25611914

  14. Retinal function and morphology are altered in cattle infected with the prion disease transmissible mink encephalopathy.

    PubMed

    Smith, J D; Greenlee, J J; Hamir, A N; Richt, J A; Greenlee, M H West

    2009-09-01

    Transmissible spongiform encephalopathies (TSEs) are a group of diseases that result in progressive and invariably fatal neurologic disease in both animals and humans. TSEs are characterized by the accumulation of an abnormal protease-resistant form of the prion protein in the central nervous system. Transmission of infectious TSEs is believed to occur via ingestion of prion protein-contaminated material. This material is also involved in the transmission of bovine spongiform encephalopathy ("mad cow disease") to humans, which resulted in the variant form of Creutzfeldt-Jakob disease. Abnormal prion protein has been reported in the retina of TSE-affected cattle, but despite these observations, the specific effect of abnormal prion protein on retinal morphology and function has not been assessed. The objective of this study was to identify and characterize potential functional and morphologic abnormalities in the retinas of cattle infected with a bovine-adapted isolate of transmissible mink encephalopathy. We used electroretinography and immunohistochemistry to examine retinas from 10 noninoculated and 5 transmissible mink encephalopathy-inoculated adult Holstein steers. Here we show altered retinal function, as evidenced by prolonged implicit time of the electroretinogram b-wave, in transmissible mink encephalopathy-infected cattle before the onset of clinical illness. We also demonstrate disruption of rod bipolar cell synaptic terminals, indicated by decreased immunoreactivity for the alpha isoform of protein kinase C and vesicular glutamate transporter 1, and activation of Müller glia, as evidenced by increased glial fibrillary acidic protein and glutamine synthetase expression, in the retinas of these cattle at the time of euthanasia due to clinical deterioration. This is the first study to identify both functional and morphologic alterations in the retinas of TSE-infected cattle. Our results support future efforts to focus on the retina for the development of

  15. Comparison of Transmissible Mink Encephalopathy Isolates in Raccoons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Owing to its susceptibility to various transmissible spongiform encephalopathies (TSE) and relatively short incubation times, the raccoon (Procyon lotor) has been suggested as a model for TSE strain differentiation. Transmissible mink encephalopathy (TME) is a prion disease of undetermined origin in...

  16. Emergence of a novel bovine spongiform encephalopathy (BSE) prion from an atypical H-type BSE

    PubMed Central

    Masujin, Kentaro; Okada, Hiroyuki; Miyazawa, Kohtaro; Matsuura, Yuichi; Imamura, Morikazu; Iwamaru, Yoshifumi; Murayama, Yuichi; Yokoyama, Takashi

    2016-01-01

    The H-type of atypical bovine spongiform encephalopathy (H-BSE) was serially passaged in bovinized transgenic (TgBoPrP) mice. At the fourth passage, most challenged mice showed a typical H-BSE phenotype with incubation periods of 223 ± 7.8 days. However, a different phenotype of BSE prion with shorter incubation periods of 109 ± 4 days emerged in a minor subset of the inoculated mice. The latter showed distinct clinical signs, brain pathology, and abnormal prion protein profiles as compared to H-BSE and other known BSE strains in mice. This novel prion was transmitted intracerebrally to cattle, with incubation periods of 14.8 ± 1.5 months, with phenotypes that differed from those of other bovine prion strains. These data suggest that intraspecies transmission of H-BSE in cattle allows the emergence of a novel BSE strain. Therefore, the continuation of feed ban programs may be necessary to exclude the recycling of H-BSE prions, which appear to arise spontaneously, in livestock. Such measures should help to reduce the risks from both novel and known strains of BSE. PMID:26948374

  17. Emergence of a novel bovine spongiform encephalopathy (BSE) prion from an atypical H-type BSE.

    PubMed

    Masujin, Kentaro; Okada, Hiroyuki; Miyazawa, Kohtaro; Matsuura, Yuichi; Imamura, Morikazu; Iwamaru, Yoshifumi; Murayama, Yuichi; Yokoyama, Takashi

    2016-01-01

    The H-type of atypical bovine spongiform encephalopathy (H-BSE) was serially passaged in bovinized transgenic (TgBoPrP) mice. At the fourth passage, most challenged mice showed a typical H-BSE phenotype with incubation periods of 223 ± 7.8 days. However, a different phenotype of BSE prion with shorter incubation periods of 109 ± 4 days emerged in a minor subset of the inoculated mice. The latter showed distinct clinical signs, brain pathology, and abnormal prion protein profiles as compared to H-BSE and other known BSE strains in mice. This novel prion was transmitted intracerebrally to cattle, with incubation periods of 14.8 ± 1.5 months, with phenotypes that differed from those of other bovine prion strains. These data suggest that intraspecies transmission of H-BSE in cattle allows the emergence of a novel BSE strain. Therefore, the continuation of feed ban programs may be necessary to exclude the recycling of H-BSE prions, which appear to arise spontaneously, in livestock. Such measures should help to reduce the risks from both novel and known strains of BSE. PMID:26948374

  18. Genetic Adaptation of Influenza A Viruses in Domestic Animals and Their Potential Role in Interspecies Transmission: A Literature Review.

    PubMed

    Munoz, Olga; De Nardi, Marco; van der Meulen, Karen; van Reeth, Kristien; Koopmans, Marion; Harris, Kate; von Dobschuetz, Sophie; Freidl, Gudrun; Meijer, Adam; Breed, Andrew; Hill, Andrew; Kosmider, Rowena; Banks, Jill; Stärk, Katharina D C; Wieland, Barbara; Stevens, Kim; van der Werf, Sylvie; Enouf, Vincent; Dauphin, Gwenaelle; Dundon, William; Cattoli, Giovanni; Capua, Ilaria

    2016-03-01

    In December 2011, the European Food Safety Authority awarded a Grant for the implementation of the FLURISK project. The main objective of FLURISK was the development of an epidemiological and virological evidence-based influenza risk assessment framework (IRAF) to assess influenza A virus strains circulating in the animal population according to their potential to cross the species barrier and cause infections in humans. With the purpose of gathering virological data to include in the IRAF, a literature review was conducted and key findings are presented here. Several adaptive traits have been identified in influenza viruses infecting domestic animals and a significance of these adaptations for the emergence of zoonotic influenza, such as shift in receptor preference and mutations in the replication proteins, has been hypothesized. Nonetheless, and despite several decades of research, a comprehensive understanding of the conditions that facilitate interspecies transmission is still lacking. This has been hampered by the intrinsic difficulties of the subject and the complexity of correlating environmental, viral and host factors. Finding the most suitable and feasible way of investigating these factors in laboratory settings represents another challenge. The majority of the studies identified through this review focus on only a subset of species, subtypes and genes, such as influenza in avian species and avian influenza viruses adapting to humans, especially in the context of highly pathogenic avian influenza H5N1. Further research applying a holistic approach and investigating the broader influenza genetic spectrum is urgently needed in the field of genetic adaptation of influenza A viruses. PMID:25630935

  19. 78 FR 73993 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-10

    ... Health Inspection Service 9 CFR Parts 92, 93, 94, 95, 96, and 98 RIN 0579-AC68 Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products Corrections In rule document 2013-28228 appearing...

  20. Prussian blue caged in spongiform adsorbents using diatomite and carbon nanotubes for elimination of cesium.

    PubMed

    Hu, Baiyang; Fugetsu, Bunshi; Yu, Hongwen; Abe, Yoshiteru

    2012-05-30

    We developed a spongiform adsorbent that contains Prussian blue, which showed a high capacity for eliminating cesium. An in situ synthesizing approach was used to synthesize Prussian blue inside diatomite cavities. Highly dispersed carbon nanotubes (CNTs) were used to form CNT networks that coated the diatomite to seal in the Prussian blue particles. These ternary (CNT/diatomite/Prussian-blue) composites were mixed with polyurethane (PU) prepolymers to produce a quaternary (PU/CNT/diatomite/Prussian-blue), spongiform adsorbent with an in situ foaming procedure. Prussian blue was permanently immobilized in the cell walls of the spongiform matrix and preferentially adsorbed cesium with a theoretical capacity of 167 mg/g cesium. Cesium was absorbed primarily by an ion-exchange mechanism, and the absorption was accomplished by self-uptake of radioactive water by the quaternary spongiform adsorbent. PMID:22464752

  1. A stochastic model of the bovine spongiform encephalopathy epidemic in Canada.

    PubMed

    Oraby, Tamer; Al-Zoughool, Mustafa; Elsaadany, Susie; Krewski, Daniel

    2016-01-01

    Bovine spongiform encephalopathy (BSE) appeared in the United Kingdom in the mid 1980s, and has been attributed to the use of meat and bone meal (MBM) in cattle feed contaminated with a scrapie-like agent. Import of infectious materials from a country where BSE has occurred is believed to be the major factor underlying the spread of the BSE epidemic to other countries. This study presents a new stochastic model developed to estimate risk of BSE from importation of cattle infected with the BSE agent. The model describes the propagation of the BSE agent through the Canadian cattle herd through rendering and feeding processes, following importation of cattle with infectious prions. This model was used estimate the annual number of newly infected animals each year over the period 1980-2019. Model predictions suggested that the number of BSE infections in Canada might have been approximately 40-fold greater than the actual number of clinically diagnosed cases. Under complete compliance with the 2007 ban on feeding MBM, this model further predicts that BSE is disappearing from the Canadian cattle system. A series of sensitivity analyses was also conducted to test the robustness of model predictions to alternative assumptions about factors affecting the evolution of the Canadian BSE epidemic. PMID:27556562

  2. Microarray analysis in caudal medulla of cattle orally challenged with bovine spongiform encephalopathy.

    PubMed

    Almeida, L M; Basu, U; Williams, J L; Moore, S S; Guan, L L

    2011-01-01

    Bovine spongiform encephalopathy (BSE) is a fatal disorder in cattle characterized by progressive neurodegeneration of the central nervous system. We investigated the molecular mechanisms involved in neurodegeneration during prion infection through the identification of genes that are differentially expressed (DE) between experimentally infected and non-challenged cattle. Gene expression of caudal medulla from control and orally infected animals was compared by microarray analysis using 24,000 bovine oligonucleotides representing 16,846 different genes to identify DE genes associated with BSE disease. In total, 182 DE genes were identified between normal and BSE-infected tissues (>2.0-fold change, P < 0.01); 81 DE genes had gene ontology functions, which included synapse function, calcium ion regulation, immune and inflammatory response, apoptosis, and cytoskeleton organization; 13 of these genes were found to be involved in 26 different Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The expression of five DE genes associated with synapse function (tachykinin, synuclein, neuropeptide Y, cocaine, amphetamine-responsive transcript, and synaptosomal-associated protein 25 kDa) and three DE genes associated with calcium ion regulation (parvalbumin, visinin-like, and cadherin) was further validated in the medulla tissue of cattle at different infection times (6, 12, 42, and 45 months post-infection) by qRT-PCR. These data will contribute to a better understanding of the molecular mechanisms of neuropathology in bovine species. PMID:22033911

  3. Experimental oral transmission of chronic wasting disease to red deer (Cervus elaphus elaphus): Early detection and late stage distribution of protease-resistant prion protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic wasting disease CWD is the transmissible spongiform encephalopathy or prion disease of wild and farmed cervid ruminants, including Rocky Mountain elk (Cervus elaphus nelsoni), white tailed deer (Odocoileus virginianus), mule deer (Odocoileus hemionus), or moose (Alces alces). Reliable data ...

  4. A history of biological disasters of animal origin in North America.

    PubMed

    Ackerman, G A; Giroux, J

    2006-04-01

    This paper examines past occurrences in North America relevant to the possibility of biological disasters with animal origins. With respect to naturally occurring animal disease outbreaks, North America, while not as adversely affected by epizootics as other regions, has had its fair share of such outbreaks of both 'traditional' and emerging animal diseases. The traditional category includes such diseases as anthrax, classical swine fever, bluetongue, brucellosis, foot and mouth disease, and the family of equine encephalomyelitis viruses. The emerging diseases include relatively more recent culprits such as postweaning multisystemic wasting syndrome, poultry enteritis mortality syndrome, and newly discovered examples of the transmissible spongiform encephalopathies. Additionally, several serious diseases of human beings that involve animal vectors or reservoirs occur naturally in North America or have emerged in recent decades; these include plague, hantavirus, monkeypox, West Nile virus and avian-derived influenza. At the same time, there have been very few intentional attacks on livestock using biological agents and no recorded cases in North America of animals intentionally being used to transmit disease to humans. According to the historical record, therefore, naturally occurring emerging zoonoses probably constitute the greatest threat in terms of biological disasters with animal origins. However, some of the general trends in terrorist activity, such as the intensification of activities by animal rights extremists against facilities undertaking animal research, mean that the possibility of intentional animal-related biological disasters should not be discounted. PMID:16796038

  5. Changes in Synaptic Transmission and Long-term Potentiation Induction as a Possible Mechanism for Learning Disability in an Animal Model of Multiple Sclerosis

    PubMed Central

    2016-01-01

    Purpose: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It has been shown that memory deficits is common in patients with MS. Recent studies using experimental autoimmune encephalomyelitis (EAE) as an animal model of MS have shown that indicated that EAE causes hippocampal-dependent impairment in learning and memory. Thus far, there have been no in vivo electrophysiological reports describing synaptic transmission in EAE animals. The aim of the present work is to evaluate the synaptic changes in the CA1 region of the hippocampus of EAE rats. Methods: To evaluate changes in synaptic transmission in the CA1 region of the hippocampus of EAE rats, field excitatory postsynaptic potentials (fEPSPs) from the stratum radiatum of CA1 neurons, were recorded following Schaffer collateral stimulation. Results: The results showed that EAE causes deficits in synaptic transmission and long-term potentiation (LTP) in the hippocampus. In addition, paired-pulse index with a 120 msec interstimulus interval was decreased in the EAE group. These findings indicate that EAE might induce suppression in synaptic transmission and LTP by increasing the inhibitory effect of GABAB receptors on the glutamate-mediated EPSP. Conclusions: In conclusion, influence of inflammation-triggered mechanisms on synaptic transmission may explain the negative effect of EAE on learning abilities in rats. PMID:27032554

  6. A pilot study for targeted surveillance of bovine spongiform encephalopathy in Nigeria.

    PubMed

    Nwankiti, O O; Ikeh, E I; Asala, O; Seuberlich, T

    2013-06-01

    Bovine spongiform encephalopathy (BSE), popularly known as 'mad cow disease', led to an epidemic in Europe that peaked in the mid-1990s. Its impact on developing countries, such as Nigeria, has not been fully established as information on livestock and surveillance has eluded those in charge of this task. The BSE risk to Nigeria's cattle population currently remains undetermined, which has resulted in international trade restrictions on commodities from the cattle population. This is mainly because of a lack of updated BSE risk assessments and disease surveillance data. To evaluate the feasibility of BSE surveillance in Nigeria, we carried out a pilot study targeting cattle that were presented for emergency or casualty slaughter. In total, 1551 cattle of local breeds, aged 24 months and above were clinically examined. Ataxia, recumbency and other neurological signs were topmost on our list of criteria. A total of 96 cattle, which correspond to 6.2%, presented clinical signs that supported a suspect of BSE. The caudal brainstem tissues of these animals were collected post-mortem and analysed for the disease-specific form of the prion protein using a rapid test approved by the International Animal Health Organization (OIE). None of the samples were positive for BSE. Although our findings do not exclude the presence of BSE in Nigeria, they do demonstrate that targeted sampling of clinically suspected cases of BSE is feasible in developing countries. In addition, these findings point to the possibility of implementing clinical monitoring schemes for BSE and potentially other diseases with grave economic and public health consequences. PMID:22594841

  7. The prion protein gene polymorphisms associated with bovine spongiform encephalopathy susceptibility differ significantly between cattle and buffalo.

    PubMed

    Zhao, Hui; Du, Yanli; Chen, Shunmei; Qing, Lili; Wang, Xiaoyan; Huang, Jingfei; Wu, Dongdong; Zhang, Yaping

    2015-12-01

    Prion protein, encoded by the prion protein gene (PRNP), plays a crucial role in the pathogenesis of transmissible spongiform encephalopathies (TSEs). Several polymorphisms within the PRNP are known to be associated with influencing bovine spongiform encephalopathy (BSE) susceptibility in cattle, namely two insertion/deletion (indel) polymorphisms (a 23-bp indel in the putative promoter and a 12-bp indel in intron 1), the number of octapeptide repeats (octarepeats) present in coding sequence (CDS) and amino acid polymorphisms. The domestic buffaloes, Bubalus bubalis, are a ruminant involved in various aspects of agriculture. It is of interest to ask whether the PRNP polymorphisms differ between cattle and buffalo. In this study, we analyzed the previously reported polymorphisms associated with BSE susceptibility in Chinese buffalo breeds, and compared these polymorphisms in cattle with BSE, healthy cattle and buffalo by pooling data from the literature. Our analysis revealed three significant findings in buffalo: 1) extraordinarily low deletion allele frequencies of the 23- and 12-bp indel polymorphisms; 2) significantly low allelic frequencies of six octarepeats in CDS and 3) the presence of S4R, A16V, P54S, G108S, V123M, S154N and F257L substitutions in buffalo CDSs. Sequence alignments comparing the buffalo coding sequence to other species were analyzed using the McDonald-Kreitman test to reveal five groups (Bison bonasus, Bos indicus, Bos gaurus, Boselaphus tragocamelus, Syncerus caffer caffer) with significantly divergent non-synonymous substitutions from buffalo, suggesting potential divergence of buffalo PRNP and others. To the best of our knowledge this is the first study of PRNP polymorphisms associated with BSE susceptibility in Chinese buffalo. Our findings have provided evidence that buffaloes have a unique genetic background in the PRNP gene in comparison with cattle. PMID:26319996

  8. Impact of potential changes to the current bovine spongiform encephalopathy surveillance programs for slaughter cattle and fallen stock in Japan.

    PubMed

    Sugiura, Katsuaki; Murray, Noel; Shinoda, Naoki; Onodera, Takashi

    2009-07-01

    Cattle slaughtered in Japan for human consumption, regardless of their age, have been tested for bovine spongiform encephalopathy (BSE) since October 2001. Beginning in April 2004, all fallen stock from 24 months of age also have been tested. We evaluated the impact of potential changes to the current BSE surveillance programs for both slaughter cattle and fallen stock using a simple stochastic model. We calculated the probability that a BSE-infected dairy cow, Wagyu beef animal, Wagyu-Holstein cross steer or heifer, or Holstein steer slaughtered for human consumption or arising as fallen stock would be tested and detected. Four surveillance strategies were explored for cattle slaughtered for human consumption, with the minimum age at testing set at 0, 21, 31, or 41 months. Three surveillance strategies were explored for fallen stock, with the minimum age at testing set at 24, 31, or 41 months. Increasing the minimum age of testing from 0 to 21 months for both dairy cattle and Wagyu beef cattle had very little impact on the probability that a BSE-infected animal slaughtered for human consumption would be detected. Although increasing the minimum age at testing from 21 to 31 or 41 months would lead to fewer slaughtered animals being tested, the impact on the probability of detecting infected animals would be insignificant. The probability of infected Wagyu-Holstein crosses and Holstein steers being detected at slaughter or as fallen stock would be very low under all surveillance strategies. PMID:19681270

  9. Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs.

    PubMed

    Chan, Jasper Fuk-Woo; Yip, Cyril Chik-Yan; Tsang, Jessica Oi-Ling; Tee, Kah-Meng; Cai, Jian-Piao; Chik, Kenn Ka-Heng; Zhu, Zheng; Chan, Chris Chung-Sing; Choi, Garnet Kwan-Yue; Sridhar, Siddharth; Zhang, Anna Jinxia; Lu, Gang; Chiu, Kin; Lo, Amy Cheuk-Yin; Tsao, Sai-Wah; Kok, Kin-Hang; Jin, Dong-Yan; Chan, Kwok-Hung; Yuen, Kwok-Yung

    2016-01-01

    Zika virus (ZIKV) is unique among human-pathogenic flaviviruses by its association with congenital anomalies and trans-placental and sexual human-to-human transmission. Although the pathogenesis of ZIKV-associated neurological complications has been reported in recent studies, key questions on the pathogenesis of the other clinical manifestations, non-vector-borne transmission and potential animal reservoirs of ZIKV remain unanswered. We systematically characterized the differential cell line susceptibility of 18 human and 15 nonhuman cell lines to two ZIKV isolates (human and primate) and dengue virus type 2 (DENV-2). Productive ZIKV replication (⩾2 log increase in viral load, ZIKV nonstructural protein-1 (NS1) protein expression and cytopathic effects (CPE)) was found in the placental (JEG-3), neuronal (SF268), muscle (RD), retinal (ARPE19), pulmonary (Hep-2 and HFL), colonic (Caco-2),and hepatic (Huh-7) cell lines. These findings helped to explain the trans-placental transmission and other clinical manifestations of ZIKV. Notably, the prostatic (LNCaP), testicular (833KE) and renal (HEK) cell lines showed increased ZIKV load and/or NS1 protein expression without inducing CPE, suggesting their potential roles in sexual transmission with persistent viral replication at these anatomical sites. Comparatively, none of the placental and genital tract cell lines allowed efficient DENV-2 replication. Among the nonhuman cell lines, nonhuman primate (Vero and LLC-MK2), pig (PK-15), rabbit (RK-13), hamster (BHK21) and chicken (DF-1) cell lines supported productive ZIKV replication. These animal species may be important reservoirs and/or potential animal models for ZIKV. The findings in our study help to explain the viral shedding pattern, transmission and pathogenesis of the rapidly disseminating ZIKV, and are useful for optimizing laboratory diagnostics and studies on the pathogenesis and counter-measures of ZIKV. PMID:27553173

  10. Infectivity in skeletal muscle of cattle with atypical bovine spongiform encephalopathy.

    PubMed

    Suardi, Silvia; Vimercati, Chiara; Casalone, Cristina; Gelmetti, Daniela; Corona, Cristiano; Iulini, Barbara; Mazza, Maria; Lombardi, Guerino; Moda, Fabio; Ruggerone, Margherita; Campagnani, Ilaria; Piccoli, Elena; Catania, Marcella; Groschup, Martin H; Balkema-Buschmann, Anne; Caramelli, Maria; Monaco, Salvatore; Zanusso, Gianluigi; Tagliavini, Fabrizio

    2012-01-01

    The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE is caused by a prion strain whose biological properties differ from those of typical BSE, resulting in a clinically and pathologically distinct phenotype. Whether peripheral tissues of BASE-affected cattle contain infectivity is unknown. This is a critical issue since the BASE prion is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible. We carried out bioassays in transgenic mice overexpressing bovine PrP (Tgbov XV) and found infectivity in a variety of skeletal muscles from cattle with natural and experimental BASE. Noteworthy, all BASE muscles used for inoculation transmitted disease, although the attack rate differed between experimental and natural cases (∼70% versus ∼10%, respectively). This difference was likely related to different prion titers, possibly due to different stages of disease in the two conditions, i.e. terminal stage in experimental BASE and pre-symptomatic stage in natural BASE. The neuropathological phenotype and PrP(res) type were consistent in all affected mice and matched those of Tgbov XV mice infected with brain homogenate from natural BASE. The immunohistochemical analysis of skeletal muscles from cattle with natural and experimental BASE showed the presence of abnormal prion protein deposits within muscle fibers. Conversely, Tgbov XV mice challenged with lymphoid tissue and kidney from natural and experimental BASE did not develop disease. The novel information on the neuromuscular tropism of the BASE strain, efficiently overcoming species barriers, underlines the relevance of maintaining an active surveillance. PMID:22363650

  11. Modeling of bovine spongiform encephalopathy in a two-species feedback loop.

    PubMed

    Barnes, Richard; Lehman, Clarence

    2013-06-01

    Bovine spongiform encephalopathy, otherwise known as mad cow disease, can spread when an individual cow consumes feed containing the infected tissues of another individual, forming a one-species feedback loop. Such feedback is the primary means of transmission for BSE during epidemic conditions. Following outbreaks in the European Union and elsewhere, many governments enacted legislation designed to limit the spread of such diseases via elimination or reduction of one-species feedback loops in agricultural systems. However, two-species feedback loops-those in which infectious material from one-species is consumed by a secondary species whose tissue is then consumed by the first species-were not universally prohibited and have not been studied before. Here we present a basic ecological disease model which examines the rôle feedback loops may play in the spread of BSE and related diseases. Our model shows that there are critical thresholds between the infection's expansion and decrease related to the lifespan of the hosts, the growth rate of the prions, and the amount of prions circulating between hosts. The ecological disease dynamics can be intrinsically oscillatory, having outbreaks as well as refractory periods which can make it appear that the disease is under control while it is still increasing. We show that non-susceptible species that have been intentionally inserted into a feedback loop to stop the spread of disease do not, strictly by themselves, guarantee its control, though they may give that appearance by increasing the refractory period of an epidemic's oscillations. We suggest ways in which age-related dynamics and cross-species coupling should be considered in continuing evaluations aimed at maintaining a safe food supply. PMID:23746801

  12. Limited transmission of emergent H7N9 influenza A virus in a simulated live animal market: Do chickens pose the principal transmission threat?

    PubMed

    Bosco-Lauth, Angela M; Bowen, Richard A; Root, J Jeffrey

    2016-08-01

    Emergent H7N9 influenza A virus has caused multiple public health and financial hardships. While some epidemiological studies have recognized infected chickens as an important bridge for human infections, the generality of this observation, the minimum infectious dose, and the shedding potential of chickens have received conflicting results. We experimentally tested the ability of domestic chickens (Gallus gallus domesticus) to transmit H7N9 to co-housed chickens and to several other animal species in an experimental live animal market. Results indicated that an infected chicken failed to initiate viral shedding of H7N9 to naïve co-housed chickens. The infected chicken did, however, successfully transmit the virus to quail (Coturnix sp.) located directly below the infected chicken cage. Oral shedding by indirectly infected quail was, on average, greater than ten-fold that of directly inoculated chickens. Best management practices in live animal market systems should consider the position of quail in stacked-cage settings. PMID:27236304

  13. 21 CFR 589.2001 - Cattle materials prohibited in animal food or feed to prevent the transmission of bovine...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to AOCS... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Cattle materials prohibited in animal food or feed... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL...

  14. 21 CFR 589.2001 - Cattle materials prohibited in animal food or feed to prevent the transmission of bovine...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to AOCS... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Cattle materials prohibited in animal food or feed... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL...

  15. Transmissibility of caprine scrapie in ovine transgenic mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Scrapie is a transmissible spongiform encephalopathy or prion disease of domestic sheep and goats. The current US and Canadian control programs are based on diagnosis by identification of abnormal prion protein in brain or lymphoid tissues with selective culling of genetically susceptible sheep exp...

  16. Consumers' understanding and concerns about bovine spongiform encephalopathy (BSE): comparison among Canadian, American, and Japanese consumers.

    PubMed

    Muringai, Violet; Goddard, Ellen; Aubeeluck, Ashwina

    2011-01-01

    In spite of much analysis of the impact of bovine spongiform encephalopathy (BSE) on consumer perceptions and meat purchases, there has been little explicit analysis of the level of BSE knowledge. In this study the role of knowledge about BSE was examined in Canada, the United States, and Japan. In addition, the level of knowledge was linked to human health concerns regarding BSE and whether there is agreement with paying a premium for beef with BSE animal tests. From a public policy perspective, understanding whether higher or lower knowledge is linked to public concern and desire for market intervention might help in the design of risk communication in any future animal disease outbreak. Should lack of knowledge about the disease be related to a public desire for market intervention (animal testing, for example), then an increase in detailed information about how humans might contract the disease might change public pressure for intervention. As compared to U.S. and Canadian respondents, Japanese respondents are more knowledgeable regarding the ways in which humans might be exposed to the human variant of BSE (variant Creutzfeldt-Jakob disease, vCJD) and are more concerned about the disease. However, U.S. respondents are more willing to pay a premium for beef tested to ensure that it will not result in vCJD. Japanese respondents who are more knowledgeable about BSE are more concerned about the risk of BSE to human health. In Canada, subjects who are more knowledgeable about the ways in which humans attain vCJD are less concerned about the risk of BSE to human health. Knowledge of the ways in which humans develop vCJD does not significantly influence concerns about the risk of BSE to human health in the United States or willingness to pay for BSE-tested beef in any of the three countries. The links between knowledge and concerns about BSE and between knowledge and agreement with paying premiums for BSE-tested beef were estimated for each country using ordered

  17. Aerosol and nasal transmission of chronic wasting disease in cervidized mice

    PubMed Central

    Denkers, Nathaniel D.; Seelig, Davis M.; Telling, Glenn C.; Hoover, Edward A.

    2010-01-01

    Little is known regarding the potential risk posed by aerosolized prions. Chronic wasting disease (CWD) is transmitted horizontally, almost surely by mucosal exposure, and CWD prions are present in saliva and urine of infected animals. However, whether CWD may be transmissible by the aerosol or nasal route is not known. To address this question, FVB mice transgenetically expressing the normal cervid PrPC protein [Tg(cerPrP) mice] were exposed to CWD prions by either nose-only aerosol exposure or by drop-wise instillation into the nostrils. Mice were monitored for signs of disease for up to 755 days post-inoculation (p.i.) and by examination of tissues for lesions and PrPCWD after necropsy. In particular, nasal mucosa, vomeronasal organ, lungs, lymphoid tissue and the brain were assessed for PrPCWD by Western blotting and immunohistochemistry. Six of seven aerosol-exposed Tg(cerPrP) mice developed clinical signs of neurological dysfunction mandating euthanasia between 411 and 749 days p.i. In all these mice, CWD infection was confirmed by detection of spongiform lesions and PrPCWD in the brain. Two of nine intranasally inoculated Tg(cerPrP) mice also developed transmissible spongiform encephalopathy associated with PrPCWD between 417 and 755 days p.i. No evidence of PrPCWD was detected in CWD-inoculated Tg(cerPrP) mice examined at pre-terminal time points. These results demonstrate that CWD can be transmitted by aerosol (as well as nasal) exposure and suggest that exposure via the respiratory system merits consideration for prion disease transmission and biosafety. PMID:20164261

  18. Global positioning system data-loggers: a tool to quantify fine-scale movement of domestic animals to evaluate potential for zoonotic transmission to an endangered wildlife population.

    PubMed

    Parsons, Michele B; Gillespie, Thomas R; Lonsdorf, Elizabeth V; Travis, Dominic; Lipende, Iddi; Gilagiza, Baraka; Kamenya, Shadrack; Pintea, Lilian; Vazquez-Prokopec, Gonzalo M

    2014-01-01

    Domesticated animals are an important source of pathogens to endangered wildlife populations, especially when anthropogenic activities increase their overlap with humans and wildlife. Recent work in Tanzania reports the introduction of Cryptosporidium into wild chimpanzee populations and the increased risk of ape mortality associated with SIVcpz-Cryptosporidium co-infection. Here we describe the application of novel GPS technology to track the mobility of domesticated animals (27 goats, 2 sheep and 8 dogs) with the goal of identifying potential routes for Cryptosporidium introduction into Gombe National Park. Only goats (5/27) and sheep (2/2) were positive for Cryptosporidium. Analysis of GPS tracks indicated that a crop field frequented by both chimpanzees and domesticated animals was a potential hotspot for Cryptosporidium transmission. This study demonstrates the applicability of GPS data-loggers in studies of fine-scale mobility of animals and suggests that domesticated animal-wildlife overlap should be considered beyond protected boundaries for long-term conservation strategies. PMID:25365070

  19. Expert elicitation as a means to attribute 28 enteric pathogens to foodborne, waterborne, animal contact, and person-to-person transmission routes in Canada.

    PubMed

    Butler, Ainslie J; Thomas, M Kate; Pintar, Katarina D M

    2015-04-01

    Enteric illness contributes to a significant burden of illness in Canada and globally. Understanding its sources is a critical step in identifying and preventing health risks. Expert elicitation is a powerful tool, used previously, to obtain information about enteric illness source attribution where information is difficult or expensive to obtain. Thirty-one experts estimated transmission of 28 pathogens via major transmission routes (foodborne, waterborne, animal contact, person-to-person, and other) at the point of consumption. The elicitation consisted of a (snowball) recruitment phase; administration of a pre-survey to collect background information, an introductory webinar, an elicitation survey, a 1-day discussion, survey readministration, and a feedback exercise, and surveys were administered online. Experts were prompted to quantify changes in contamination at the point of entry into the kitchen versus point of consumption. Estimates were combined via triangular probability distributions, and medians and 90% credible-interval estimates were produced. Transmission was attributed primarily to food for Bacillus cereus, Clostridium perfringens, Cyclospora cayetanensis, Trichinella spp., all three Vibrio spp. categories explored, and Yersinia enterocolitica. Multisource pathogens (e.g., transmitted commonly through both water and food) such as Campylobacter spp., four Escherichia coli categories, Listeria monocytogenes, Salmonella spp., and Staphylococcus aureus were also estimated as mostly foodborne. Water was the primary pathway for Giardia spp. and Cryptosporidium spp., and person-to-person transmission dominated for six enteric viruses and Shigella spp. Consideration of the point of attribution highlighted the importance of food handling and cross-contamination in the transmission pathway. This study provides source attribution estimates of enteric illness for Canada, considering all possible transmission routes. Further research is necessary to improve our

  20. Bovine spongiform encephalopathy: are the cows mad or full of carbohydrates?

    PubMed

    Frey, Jacques

    2002-02-01

    The non-forage feeding of dairy cows rich in fast absorption carbohydrates, the low value of their euglycemic-hyperinsulinemic clamp suggest a dysregulation of carbohydrate metabolism able to produce neurodegenerative disorders. Comparisons between Alzheimer's disease developed in diabetes mellitus and bovine spongiform encephalopathy (BSE) direct the discussion of the origin of BSE not only towards a contamination by prion proteins. PMID:11939480

  1. Comparative aspects of bovine spongiform encephalopathy isolates found in the U.S.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE) can be subdivided into at least three groups: classical, H-type, and L-type. The latter 2 designations are based on higher or lower apparent molecular mass profiles of the unglycosylated PrP**Sc band in a western blot and are collectively referred to as atypica...

  2. 78 FR 11207 - Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-15

    ... to discuss FDA's draft risk assessment model for potential exposure to the variant Creutzfeldt-Jakob disease (vCJD) agent in Red Blood Cells for transfusion in the United States. FDA intends to...

  3. 75 FR 55803 - Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... agents from blood components and chronic wasting disease. FDA intends to make background material... the variant Creutzfeldt-Jakob disease (vCJD) agent in U.S.-licensed plasma-derived Factor VIII and...

  4. Methicillin (Oxacillin)-resistant Staphylococcus aureus strains isolated from major food animals and their potential transmission to humans.

    PubMed

    Lee, John Hwa

    2003-11-01

    From May 2001 to April 2003, various types of specimens from cattle, pigs, and chickens were collected and examined for the presence of methicillin (oxacillin)-resistant Staphylococcus aureus (MRSA). S. aureus was isolated and positively identified by using Gram staining, colony morphology, tests for coagulase and urease activities, and an API Staph Ident system. Among 1,913 specimens collected from the animals, 421 contained S. aureus; of these, 28 contained S. aureus resistant to concentrations of oxacillin higher than 2 micro g/ml. Isolates from 15 of the 28 specimens were positive by PCR for the mecA gene. Of the 15 mecA-positive MRSA isolates, 12 were from dairy cows and 3 were from chickens. Antimicrobial susceptibility tests of mecA-positive MRSA strains were performed by the disk diffusion method. All isolates were resistant to members of the penicillin family, such as ampicillin, oxacillin, and penicillin. All isolates were also susceptible to amikacin, vancomycin, and trimethoprim-sulfamethoxazole. To determine molecular epidemiological relatedness of these 15 animal MRSA isolates to isolates from humans, random amplified polymorphic DNA (RAPD) patterns were generated by arbitrarily primed PCR. The RAPD patterns of six of the isolates from animals were identical to the patterns of certain isolates from humans. The antibiotypes of the six animal isolates revealed types similar to those of the human isolates. These data suggested that the genomes of the six animal MRSA isolates were very closely related to those of some human MRSA isolates and were a possible source of human infections caused by consuming contaminated food products made from these animals. PMID:14602604

  5. Long-term impacts of bovine spongiform encephalopathy on beef risk perceptions and risk attitudes in Canada.

    PubMed

    Muringai, Violet; Goddard, Ellen

    2016-01-01

    In this study, the objective was to examine whether or not changes in bovine spongiform encephalopathy (BSE) concerns exert an effect on people's risk perceptions and risk attitudes regarding consuming beef in Canada, 8 years after finding the first domestic animal with BSE. Data were collected from two surveys (2071 respondents) conducted with the same respondents in 2008 and 2011 in Canada. Data on meat consumption for the same households were also available from the Nielsen Homescan panel over the period 2002 to 2009. Based on census data, the current sample is generally not representative of the Canadian population, but the sample is unique in that the same individuals responded to two surveys and there is an ability to track their evolving household purchases of beef before the first survey and between the two surveys. In essence, alterations in beef risk perceptions are significantly influenced by changes in concerns regarding (1) feed given to livestock, (2) animal diseases and BSE, (3) trust in manufacturers, the government, and farmers, and (4) demographic characteristics. There were significant differences in beef purchases across households, with alterations to their risk perceptions and risk attitudes. In conclusion, although the first domestic incident of BSE was in 2003, concerns regarding BSE are still contributing to consumers' risk perceptions but not to their risk attitudes with respect to consumption of beef in 2011. PMID:27556567

  6. 21 CFR 589.2001 - Cattle materials prohibited in animal food or feed to prevent the transmission of bovine...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to AOCS... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS...; (iii) The entire carcass of cattle not inspected and passed for human consumption as defined...

  7. 21 CFR 589.2001 - Cattle materials prohibited in animal food or feed to prevent the transmission of bovine...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to AOCS... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS...; (iii) The entire carcass of cattle not inspected and passed for human consumption as defined...

  8. 21 CFR 589.2001 - Cattle materials prohibited in animal food or feed to prevent the transmission of bovine...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... 552(a) and 1 CFR part 51, or another method equivalent in accuracy, precision, and sensitivity to AOCS... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS...; (iii) The entire carcass of cattle not inspected and passed for human consumption as defined...

  9. Molecular characterisation of Galba truncatula, Lymnaea neotropica and L. schirazensis from Cajamarca, Peru and their potential role in transmission of human and animal fascioliasis

    PubMed Central

    2012-01-01

    Background Human and animal fascioliasis is emerging in many world regions, among which Andean countries constitute the largest regional hot spot and Peru the country presenting more human endemic areas. A survey was undertaken on the lymnaeid snails inhabiting the hyperendemic area of Cajamarca, where human prevalences are the highest known among the areas presenting a "valley transmission pattern", to establish which species are present, genetically characterise their populations by comparison with other human endemic areas, and discuss which ones have transmission capacity and their potential implications with human and animal infection. Methods Therefore, ribosomal DNA ITS-2 and ITS-1, and mitochondrial DNA 16S and cox1 were sequenced by the dideoxy chain-termination method. Results Results indicate the presence of three, morphologically similar, small lymnaeid species belonging to the Galba/Fossaria group: Galba truncatula, Lymnaea neotropica and L. schirazensis. Only one combined haplotype for each species was found. The ITS-1, 16S and cox1 haplotypes of G. truncatula are new. No new haplotypes were found in the other two species. This scenario changes previous knowledge, in which only L. viator (= L. viatrix) was mentioned. Galba truncatula appears to be the most abundant, with high population densities and evident anthropophyly including usual presence in human neighbourhood. Infection by Fasciola hepatica larval stages were molecularly confirmed in two populations of this species. The nearness between G. truncatula populations presenting liver fluke infection and both human settings and schools for children, together with the absence of populations of other lymnaeid species in the locality, suggest a direct relationship with human infection. Conclusions The geographical overlap of three lymnaeid species poses problems for epidemiological studies and control action. First, a problem in classifying lymnaeid specimens in both field and laboratory activities

  10. g-FLUA2H: a web-based application to study the dynamics of animal-to-human mutation transmission for influenza viruses

    PubMed Central

    2015-01-01

    g-FLUA2H is a web-based application focused on the analysis of the dynamics of influenza virus animal-to-human (A2H) mutation transmissions. The application only requires the viral protein sequences from both the animal and human host populations as input datasets. The comparative analyses between the co-aligned sequences of the two viral populations is based on a sliding window approach of size nine for statistical significance and data application to the major histocompatibility complex (MHC) and T-cell receptor (TCR) immune response mechanisms. The sequences at each of the aligned overlapping nonamer positions for the respective virus hosts are classified as four patterns of characteristic diversity motifs, as a basis for quantitative analyses: (i) "index", the most prevalent sequence; (ii) "major" variant, the second most common sequence and the single most prevalent variant of the index, with at least one amino acid mutation; (iii) "minor" variants, multiple different sequences, each with an incidence (percent occurrence) less than that of the major variant; and (iv) "unique" variants, each with only one occurrence in the alignment. The diversity motifs and their incidences at each of the nonamer positions allow evaluation of the mutation transmission dynamics and selectivity of the viral sequences in relation to the animal and the human hosts. g-FLUA2H is facilitated by a grid back-end for parallel processing of large sequence datasets. The web-application is publicly available at http://bioinfo.perdanauniversity.edu.my/g-FLUA2H. It can be used for a detailed characterization of the composition and incidence of mutations present in the proteomes of influenza viruses from animal and human host populations, for a better understanding of host tropism. PMID:26680743

  11. The role of animal movement, including off-farm rearing of heifers, in the interherd transmission of multidrug-resistant Salmonella.

    PubMed

    Adhikari, B; Besser, T E; Gay, J M; Fox, L K; Davis, M A; Cobbold, R N; Berge, A C B; Hancock, D D

    2009-09-01

    Fifty-nine commercial dairy farms were sampled 7 times over 15 to 21 mo to determine the role of animal movement, including off-farm rearing of heifers, in the interherd transmission of multidrug-resistant (MDR) Salmonella spp. Farm management data were collected by on-site inspections and questionnaires on herd management practices before and after the study. Forty-four percent (26/59) of herds did not acquire any new MDR Salmonella strains. The number of newly introduced MDR Salmonella strains acquired by the remaining 56% (33/59) of herds ranged from 1 to 8. Logistic regression models indicated that off-farm heifer raising, including contract heifer raising where heifers commingle with cattle from other farms [commingled heifers, odds ratio (OR) = 8.9, 95% confidence interval (CI): 2.4, 32.80], and herd size per 100-animal increment (herd size, OR = 1.04, 95% CI, 1.01, 1.05) were significantly associated with the introduction of new MDR Salmonella strains. The negative binomial regression similarly revealed that commingled heifers [relative risk (RR) = 2.3, 95% CI: 1.1, 4.7], herd size per 100 animals (RR = 1.02, 95% CI, 1.01, 1.03), and a history of clinical salmonellosis diagnosed before the study (RR = 2.5, 95% CI, 1.3, 5.0) were significantly associated with the number of new MDR Salmonella strains that were introduced. Factors not associated with the introduction of new MDR Salmonella strains were housing of heifers and cows in the same close-up pen, a common hospital-maternity pen, and the number of purchased cattle. This study highlights the role of animal movement in the interherd transmission of MDR Salmonella spp. PMID:19700684

  12. Genetic Analysis of the Gdh and Bg Genes of Animal-Derived Giardia duodenalis Isolates in Northeastern China and Evaluation of Zoonotic Transmission Potential

    PubMed Central

    Shen, Yujuan; Zhang, Weizhe; Wang, Rongjun; Zhao, Wei; Zhang, Longxian; Ling, Hong; Cao, Jianping

    2014-01-01

    Background Giardia duodenalis is a common intestinal parasite that infects humans and many other mammals, mainly distributing in some areas with poor sanitation. The proportion of the human giardiasis burden attributable to G. duodenalis of animal origin differs in different geographical areas. In Mainland China, genetic data of the gdh and bg genes of G. duodenalis from animals are only limited in dogs and cats. The aim of the study was to provide information on the genetic characterizations of animal-derived G. duodenalis isolates (from rabbits, sheep and cattle) at both loci in Heilongjiang Province, Northeastern China, and to assess the potential for zoonotic transmission. Methodology/Principal Findings 61 G. duodenalis isolates from animal feces (dairy and beef cattle, sheep and rabbits) in Heilongjiang Province were characterized at the gdh and bg loci in the present study. The gdh and bg gene sequences of sheep-derived G. duodenalis assemblage AI, and the gdh sequences of rabbit-derived G. duodenalis assemblage B had 100% similarity with those from humans, respectively. Novel subtypes of G. duodenalis were identified, with one and seven subtypes for assemblages A and E at the gdh locus, and two and three subtypes for assemblages B and E at the bg locus, respectively. Three pairs of the same bg sequences of assemblage E were observed in sheep and cattle. Conclusions/Significance This is the first description of genetic characterizations of the gdh and bg genes of G. duodenalis from rabbits, sheep and cattle in Mainland China. Homology analysis of assemblages AI and B implied the possibility of zoonotic transmission. The novel subtypes of assemblages of G. duodenalis may represent the endemic genetic characteristics of G. duodenalis in Heilongjiang Province, China. PMID:24748379

  13. Global Positioning System Data-Loggers: A Tool to Quantify Fine-Scale Movement of Domestic Animals to Evaluate Potential for Zoonotic Transmission to an Endangered Wildlife Population

    PubMed Central

    Parsons, Michele B.; Gillespie, Thomas R.; Lonsdorf, Elizabeth V.; Travis, Dominic; Lipende, Iddi; Gilagiza, Baraka; Kamenya, Shadrack; Pintea, Lilian; Vazquez-Prokopec, Gonzalo M.

    2014-01-01

    Domesticated animals are an important source of pathogens to endangered wildlife populations, especially when anthropogenic activities increase their overlap with humans and wildlife. Recent work in Tanzania reports the introduction of Cryptosporidium into wild chimpanzee populations and the increased risk of ape mortality associated with SIVcpz-Cryptosporidium co-infection. Here we describe the application of novel GPS technology to track the mobility of domesticated animals (27 goats, 2 sheep and 8 dogs) with the goal of identifying potential routes for Cryptosporidium introduction into Gombe National Park. Only goats (5/27) and sheep (2/2) were positive for Cryptosporidium. Analysis of GPS tracks indicated that a crop field frequented by both chimpanzees and domesticated animals was a potential hotspot for Cryptosporidium transmission. This study demonstrates the applicability of GPS data-loggers in studies of fine-scale mobility of animals and suggests that domesticated animal–wildlife overlap should be considered beyond protected boundaries for long-term conservation strategies. PMID:25365070

  14. Detection and discrimination of classical and atypical L-type bovine spongiform encephalopathy by real-time quaking-induced conversion.

    PubMed

    Orrú, Christina D; Favole, Alessandra; Corona, Cristiano; Mazza, Maria; Manca, Matteo; Groveman, Bradley R; Hughson, Andrew G; Acutis, Pier Luigi; Caramelli, Maria; Zanusso, Gianluigi; Casalone, Cristina; Caughey, Byron

    2015-04-01

    Statutory surveillance of bovine spongiform encephalopathy (BSE) indicates that cattle are susceptible to both classical BSE (C-BSE) and atypical forms of BSE. Atypical forms of BSE appear to be sporadic and thus may never be eradicated. A major challenge for prion surveillance is the lack of sufficiently practical and sensitive tests for routine BSE detection and strain discrimination. The real-time quaking-induced conversion (RT-QuIC) test, which is based on prion-seeded fibrillization of recombinant prion protein (rPrPSen), is known to be highly specific and sensitive for the detection of multiple human and animal prion diseases but not BSE. Here, we tested brain tissue from cattle affected by C-BSE and atypical L-type bovine spongiform encephalopathy (L-type BSE or L-BSE) with the RT-QuIC assay and found that both BSE forms can be detected and distinguished using particular rPrPSen substrates. Specifically, L-BSE was detected using multiple rPrPSen substrates, while C-BSE was much more selective. This substrate-based approach suggests a diagnostic strategy for specific, sensitive, and rapid detection and discrimination of at least some BSE forms. PMID:25609728

  15. Complex proteinopathy with accumulations of prion protein, hyperphosphorylated tau, α-synuclein and ubiquitin in experimental bovine spongiform encephalopathy of monkeys

    PubMed Central

    Cervenak, Juraj; Bu, Ming; Miller, Lindsay; Asher, David M.

    2014-01-01

    Proteins aggregate in several slowly progressive neurodegenerative diseases called ‘proteinopathies’. Studies with cell cultures and transgenic mice overexpressing mutated proteins suggested that aggregates of one protein induced misfolding and aggregation of other proteins as well – a possible common mechanism for some neurodegenerative diseases. However, most proteinopathies are ‘sporadic’, without gene mutation or overexpression. Thus, proteinopathies in WT animals genetically close to humans might be informative. Squirrel monkeys infected with the classical bovine spongiform encephalopathy agent developed an encephalopathy resembling variant Creutzfeldt–Jakob disease with accumulations not only of abnormal prion protein (PrPTSE), but also three other proteins: hyperphosphorylated tau (p-tau), α-synuclein and ubiquitin; β-amyloid protein (Aβ) did not accumulate. Severity of brain lesions correlated with spongiform degeneration. No amyloid was detected. These results suggested that PrPTSE enhanced formation of p-tau and aggregation of α-synuclein and ubiquitin, but not Aβ, providing a new experimental model for neurodegenerative diseases associated with complex proteinopathies. PMID:24769839

  16. Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein.

    PubMed

    Lasmézas, C I; Deslys, J P; Robain, O; Jaegly, A; Beringue, V; Peyrin, J M; Fournier, J G; Hauw, J J; Rossier, J; Dormont, D

    1997-01-17

    The agent responsible for transmissible spongiform encephalopathies (TSEs) is thought to be a malfolded, protease-resistant version (PrPres) of the normal cellular prion protein (PrP). The interspecies transmission of bovine spongiform encephalopathy (BSE) to mice was studied. Although all of the mice injected with homogenate from BSE-infected cattle brain exhibited neurological symptoms and neuronal death, more than 55 percent had no detectable PrPres. During serial passage, PrPres appeared after the agent became adapted to the new host. Thus, PrPres may be involved in species adaptation, but a further unidentified agent may actually transmit BSE. PMID:8994041

  17. Use of substances of animal origin in pharmaceutics and compliance with the TSE-risk guideline -- a market survey.

    PubMed

    Berger, Christoph N; Le Donne, Patrizia; Windemann, Helena

    2005-03-01

    The risk of infection with transmissible spongiform encephalopathy (TSE) from the use of animal-derived substances in drug manufacturing was assessed [Swissmedic. TSE guideline to the ordinance. 2001; http://www.swissmedic.ch/files/pdf/Anleitung_TSE.pdf; The European Directorate for the Quality of Medicines. Minimising the risk of transmitting animal spongiform encephalopathy agents via medicinal products. In: European Pharmacopoeia 2002; General chapter 5.2.8. http://www.pheur.org/medias/download/50208E.pdf]. In addition, the compliance of the Swiss Market Authorisation holders to implement the Swissmedic TSE guidelines was examined. To assess the compliance with the TSE guideline for products on the Swiss market a representative number of drugs were selected based on a statistical approach. The documents for the biological, anatomical and geographical origin of the animal substances used for drug manufacturing as well as for the manufacturing processes were requested to be provided within a short response period and were subsequently reviewed. A total of 438 drugs with 655 substances of animal origin were assessed during the survey. The documentation provided by the Market Authorisation holders showed, that in general the measures described in the TSE guidelines were implemented well. Therefore, the risk of these pharmaceutics to transmit TSE was considered minimized. However, the TSE documentation provided by drug companies was incomplete for approximately two-third of the drugs at the beginning of the survey. In particular for those containing excipients such as tallow derivatives or gelatine, numerous clarifications were needed prior assessment. The efforts of the drug companies to correspond to regulatory actions and to implement authoritative guidelines should be improved. PMID:15713551

  18. Meat and bone meal and mineral feed additives may increase the risk of oral prion disease transmission

    USGS Publications Warehouse

    Johnson, Christopher J.; McKenzie, Debbie; Pedersen, Joel A.; Aiken, Judd M.

    2011-01-01

    Ingestion of prion-contaminated materials is postulated to be a primary route of prion disease transmission. Binding of prions to soil (micro)particles dramatically enhances peroral disease transmission relative to unbound prions, and it was hypothesized that micrometer-sized particles present in other consumed materials may affect prion disease transmission via the oral route of exposure. Small, insoluble particles are present in many substances, including soil, human foods, pharmaceuticals, and animal feeds. It is known that meat and bone meal (MBM), a feed additive believed responsible for the spread of bovine spongiform encephalopathy (BSE), contains particles smaller than 20 μm and that the pathogenic prion protein binds to MBM. The potentiation of disease transmission via the oral route by exposure to MBM or three micrometer-sized mineral feed additives was determined. Data showed that when the disease agent was bound to any of the tested materials, the penetrance of disease was increased compared to unbound prions. Our data suggest that in feed or other prion-contaminated substances consumed by animals or, potentially, humans, the addition of MBM or the presence of microparticles could heighten risks of prion disease acquisition.

  19. Meat and bone meal and mineral feed additives may increase the risk of oral prion disease transmission

    USGS Publications Warehouse

    Johnson, C.J.; McKenzie, D.; Pedersen, J.A.; Aiken, Judd M.

    2011-01-01

    Ingestion of prion-contaminated materials is postulated to be a primary route of prion disease transmission. Binding of prions to soil (micro)particles dramatically enhances peroral disease transmission relative to unbound prions, and it was hypothesized that micrometer-sized particles present in other consumed materials may affect prion disease transmission via the oral route of exposure. Small, insoluble particles are present in many substances, including soil, human foods, pharmaceuticals, and animal feeds. It is known that meat and bone meal (MBM), a feed additive believed responsible for the spread of bovine spongiform encephalopathy (BSE), contains particles smaller than 20 ??m and that the pathogenic prion protein binds to MBM. The potentiation of disease transmission via the oral route by exposure to MBM or three micrometer-sized mineral feed additives was determined. Data showed that when the disease agent was bound to any of the tested materials, the penetrance of disease was increased compared to unbound prions. Our data suggest that in feed or other prion-contaminated substances consumed by animals or, potentially, humans, the addition of MBM or the presence of microparticles could heighten risks of prion disease acquisition. Copyright ?? 2011 Taylor & Francis Group, LLC.

  20. Transmission of scrapie prions to primate after an extended silent incubation period

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Classical bovine spongiform encephalopathy (c-BSE) is an animal prion disease that also causes variant Creutzfeldt-Jakob disease in humans. Over the past decades, c-BSE's zoonotic potential has been the driving force in establishing extensive protective measures for animal and human health. In compl...

  1. Efficient Transmission and Characterization of Creutzfeldt–Jakob Disease Strains in Bank Voles

    PubMed Central

    Nonno, Romolo; Bari, Michele A. Di; Cardone, Franco; Vaccari, Gabriele; Fazzi, Paola; Dell'Omo, Giacomo; Cartoni, Claudia; Ingrosso, Loredana; Boyle, Aileen; Galeno, Roberta; Sbriccoli, Marco; Lipp, Hans-Peter; Bruce, Moira; Pocchiari, Maurizio; Agrimi, Umberto

    2006-01-01

    Transmission of prions between species is limited by the “species barrier,” which hampers a full characterization of human prion strains in the mouse model. We report that the efficiency of primary transmission of prions from Creutzfeldt–Jakob disease patients to a wild rodent species, the bank vole (Clethrionomys glareolus), is comparable to that reported in transgenic mice carrying human prion protein, in spite of a low prion protein–sequence homology between man and vole. Voles infected with sporadic and genetic Creutzfeldt–Jakob disease isolates show strain-specific patterns of spongiform degeneration and pathological prion protein–deposition, and accumulate protease-resistant prion protein with biochemical properties similar to the human counterpart. Adaptation of genetic Creutzfeldt–Jakob disease isolates to voles shows little or no evidence of a transmission barrier, in contrast to the striking barriers observed during transmission of mouse, hamster, and sheep prions to voles. Our results imply that in voles there is no clear relationship between the degree of homology of the prion protein of the donor and recipient species and susceptibility, consistent with the view that the prion strain gives a major contribution to the species barrier. The vole is therefore a valuable model to study human prion diversity and, being susceptible to a range of animal prions, represents a unique tool for comparing isolates from different species. PMID:16518470

  2. Role of the draining lymph node in scrapie agent transmission from the skin.

    PubMed

    Glaysher, Bridget R; Mabbott, Neil A

    2007-03-15

    Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that affect humans and animals. Diseases include scrapie in sheep and Creutzfeldt-Jakob disease in humans. Following peripheral exposure, TSE agents usually accumulate on follicular dendritic cells (FDCs) in lymphoid tissues before neuroinvasion. Studies in mice have shown that TSE exposure through scarified skin is an effective means of transmission. Following inoculation by this route TSE agent accumulation upon FDCs is likewise essential for the subsequent transmission of disease to the brain. However, which lymphoid tissues are crucial for TSE pathogenesis following inoculation via the skin was not known. Mice were therefore created that lacked the draining inguinal lymph node (ILN), but had functional FDCs in remaining lymphoid tissues such as the spleen. These mice were inoculated with the scrapie agent by skin scarification to allow the role of draining ILN in scrapie pathogenesis to be determined. We show that following inoculation with the scrapie agent by skin scarification, disease susceptibility was dramatically reduced in mice lacking the draining ILN. These data demonstrate that following inoculation by skin scarification, scrapie agent accumulation upon FDCs in the draining lymph node is critical for the efficient transmission of disease to the brain. PMID:17292972

  3. Mucosal transmission and pathogenesis of chronic wasting disease in ferrets.

    PubMed

    Perrott, Matthew R; Sigurdson, Christina J; Mason, Gary L; Hoover, Edward A

    2013-02-01

    Chronic wasting disease (CWD) of cervids is almost certainly transmitted by mucosal contact with the causative prion, whether by direct (animal-to-animal) or indirect (environmental) means. Yet the sites and mechanisms of prion entry remain to be further understood. This study sought to extend this understanding by demonstrating that ferrets exposed to CWD via several mucosal routes developed infection, CWD prion protein (PrP(CWD)) amplification in lymphoid tissues, neural invasion and florid transmissible spongiform encephalopathy lesions resembling those in native cervid hosts. The ferrets developed extensive PrP(CWD) accumulation in the nervous system, retina and olfactory epithelium, with lesser deposition in tongue, muscle, salivary gland and the vomeronasal organ. PrP(CWD) accumulation in mucosal sites, including upper respiratory tract epithelium, olfactory epithelium and intestinal Peyer's patches, make the shedding of prions by infected ferrets plausible. It was also observed that regionally targeted exposure of the nasopharyngeal mucosa resulted in an increased attack rate when compared with oral exposure. The latter finding suggests that nasal exposure enhances permissiveness to CWD infection. The ferret model has further potential for investigation of portals for initiation of CWD infection. PMID:23100363

  4. Disease-associated prion protein in neural and lymphoid tissues of mink (Mustela vison) inoculated with transmissible mink encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transmissible mink encephalopathy (TME) is a prion disorder of farmed raised mink. As with the other transmissible spongiform encephalopathies, the disorder is associated with accumulation of the misfolded prion protein in the brain and an invariably fatal outcome. TME outbreaks have been rare but...

  5. Pathogenesis of experimental bovine spongiform encephalopathy (BSE): estimation of tissue infectivity according to incubation period§

    PubMed Central

    Arnold, Mark Edward; Hawkins, Stephen Anthony Charles; Green, Robert; Dexter, Ian; Wells, Gerald Arthur Henry

    2009-01-01

    This paper reports the results of tissue infectivity assays of bovine spongiform encephalopathy (BSE) agent in orally exposed cattle at stages during the incubation period. Estimations of the titre of infectivity in central nervous system (CNS), certain peripheral nerve ganglia and distal ileum tissue were made according to time post exposure from the relationship between incubation period and dose for RIII mice and C57bl mice using data from titrations of brain material from cases of BSE. The rate of increase of infectivity in the bovine CNS was then estimated, taking into account these tissue infectivity titres, the variability of the brain titre of clinical field cases of BSE, and the probability density of the expected number of months before clinical onset of each infected bovine. The doubling time for CNS was shown to equal 1.2 months. The titre in the thoracic dorsal root ganglia (DRG) was, on average, approximately 1 log units less than CNS, and cervical DRG approximately 0.5 log less than thoracic DRG. The pattern of increase of infectivity in the distal ileum is that of an initial increase up to 14–18 months post exposure, followed by a decrease, which is likely to be highly variable between animals. These results will be informative for future risk assessments of BSE, especially in relation to reviewing current control measures. PMID:18950589

  6. Rapid assessment of bovine spongiform encephalopathy prion inactivation by heat treatment in yellow grease produced in the industrial manufacturing process of meat and bone meals

    PubMed Central

    2013-01-01

    Background Prions, infectious agents associated with transmissible spongiform encephalopathy, are primarily composed of the misfolded and pathogenic form (PrPSc) of the host-encoded prion protein. Because PrPSc retains infectivity after undergoing routine sterilizing processes, the cause of bovine spongiform encephalopathy (BSE) outbreaks are suspected to be feeding cattle meat and bone meals (MBMs) contaminated with the prion. To assess the validity of prion inactivation by heat treatment in yellow grease, which is produced in the industrial manufacturing process of MBMs, we pooled, homogenized, and heat treated the spinal cords of BSE-infected cows under various experimental conditions. Results Prion inactivation was analyzed quantitatively in terms of the infectivity and PrPSc of the treated samples. Following treatment at 140°C for 1 h, infectivity was reduced to 1/35 of that of the untreated samples. Treatment at 180°C for 3 h was required to reduce infectivity. However, PrPSc was detected in all heat-treated samples by using the protein misfolding cyclic amplification (PMCA) technique, which amplifies PrPScin vitro. Quantitative analysis of the inactivation efficiency of BSE PrPSc was possible with the introduction of the PMCA50, which is the dilution ratio of 10% homogenate needed to yield 50% positivity for PrPSc in amplified samples. Conclusions Log PMCA50 exhibited a strong linear correlation with the transmission rate in the bioassay; infectivity was no longer detected when the log PMCA50 of the inoculated sample was reduced to 1.75. The quantitative PMCA assay may be useful for safety evaluation for recycling and effective utilization of MBMs as an organic resource. PMID:23835086

  7. Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: how safe is eating beef?

    PubMed

    Roma, Andres A; Prayson, Richard A

    2005-03-01

    Cases of bovine spongiform encephalopathy (BSE, mad cow disease) have been found in North American cattle. Its human counterpart, called variant Creutzfeldt-Jakob disease (variant CJD), is rare but seems to be linked to eating diseased beef. Many questions remain about these diseases, such as why young people seem at greater risk of variant CJD. Also, are some people more genetically at risk for acquiring variant CJD than others? PMID:15825799

  8. EXPERIMENTAL TRANSMISSION OF CHRONIC WASTING DISEASE (CWD) OF ELK (CERVUS ELAPHUS NELSONI), WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS), AND MULE DEER (ODOCOILEUS HEMIONUS HEMIONUS) TO WHITE-TAILED DEER BY INTRACEREBRAL ROUTE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) affecting elk, white-tailed deer, and mule deer. Intra-species transmission of CWD is readily accomplished via oral administration of CWD-affected brain. And while the exact mode of natural transmission is unclear, ho...

  9. Experimental Inoculation of Spiroplasma mirum and Transmissible Mink Encephalopathy (TME) into Raccoons (Procyon lotor)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine if Spiroplasma mirum would be capable of producing lesions of spongiform encephalopathy in raccoons (Procyon lotor), 5 groups (n = 5) of raccoon kits were inoculated intracerebrally with either S. mirum and/or transmissible mink encephalopathy (TME). Two other groups (n = 5) of raccoon...

  10. Experimental transmission of U.S. scrapie agent to neonatal sheep by oral route

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Scrapie, a transmissible spongiform encephalopathy (TSE), is a naturally occurring fatal neurodegenerative disease of sheep and goats. This study documents incubation periods, pathological findings and distribution of abnormal prion proteins (PrP**Sc) by immunohistochemistry and Western blot in tiss...

  11. A species barrier limits transmission of chronic wasting disease to mink (Mustela vison)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Transmissible Mink Encephalopathy (TME) occurs as sporadic outbreaks associated with ingestion of feed presumably contaminated with some type of prion disease. Mink lack a species barrier to primary oral challenge with Bovine Spongiform Encephalopathy, whereas they have a barrier to such challenge ...

  12. Experimental oral transmission of chronic wasting disease to reindeer (Rangifer tarandus tarandus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy or TSE of wild and farmed cervid ruminants in the North America, including white tailed, black tailed and mule deer, Rocky Mountain elk and Shira's moose. CWD, like the other TSEs, is associated with accumulation of an abnorm...

  13. Simulation of between-farm transmission of porcine reproductive and respiratory syndrome virus in Ontario, Canada using the North American Animal Disease Spread Model.

    PubMed

    Thakur, Krishna K; Revie, Crawford W; Hurnik, Daniel; Poljak, Zvonimir; Sanchez, Javier

    2015-03-01

    Porcine reproductive and respiratory syndrome (PRRS), a viral disease of swine, has major economic impacts on the swine industry. The North American Animal Disease Spread Model (NAADSM) is a spatial, stochastic, farm level state-transition modeling framework originally developed to simulate highly contagious and foreign livestock diseases. The objectives of this study were to develop a model to simulate between-farm spread of a homologous strain of PRRS virus in Ontario swine farms via direct (animal movement) and indirect (sharing of trucks between farms) contacts using the NAADSM and to compare the patterns and extent of outbreak under different simulated conditions. A total of 2552 swine farms in Ontario province were allocated to each census division of Ontario and geo-locations of the farms were randomly generated within the agriculture land of each Census Division. Contact rates among different production types were obtained using pig movement information from four regions in Canada. A total of 24 scenarios were developed involving various direct (movement of infected animals) and indirect (pig transportation trucks) contact parameters in combination with alternating the production type of the farm in which the infection was seeded. Outbreaks were simulated for one year with 1000 replications. The median number of farms infected, proportion of farms with multiple outbreaks and time to reach the peak epidemic were used to compare the size, progression and extent of outbreaks. Scenarios involving spread only by direct contact between farms resulted in outbreaks where the median percentage of infected farms ranged from 31.5 to 37% of all farms. In scenarios with both direct and indirect contact, the median percentage of infected farms increased to a range from 41.6 to 48.6%. Furthermore, scenarios with both direct and indirect contact resulted in a 44% increase in median epidemic size when compared to the direct contact scenarios. Incorporation of both animal

  14. 9 CFR 94.11 - Restrictions on importation of meat and other animal products from specified regions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume and... DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE SPONGIFORM... animal products from specified regions. (a) The meat of ruminants or swine, and other animal...

  15. Animal-assisted therapy with children suffering from insecure attachment due to abuse and neglect: a method to lower the risk of intergenerational transmission of abuse?

    PubMed

    Parish-Plass, Nancy

    2008-01-01

    Children suffering from insecure attachment due to severe abuse and/or neglect are often characterized by internal working models which, although perhaps adaptive within the original family situation, are inappropriate and maladaptive in other relationships and situations. Such children have a higher probability than the general population of becoming abusing or neglecting parents. Besides the usual goals of psychotherapy, an overall goal is to stop the cycle of abuse in which abused children may grow up to be abusing parents. Therapy with these children is complicated by their distrust in adults as well as difficulties in symbolization due to trauma during the preverbal stage. Animal-Assisted Therapy (AAT) provides avenues for circumventing these difficulties, as well as providing additional tools for reaching the inner world of the client. This article gives a brief background of the connection between insecure attachment and intergenerational transmission of abuse and neglect as well as a brief overview of the principles of AAT in a play therapy setting. A rationale for the use of AAT as a unique therapy technique for children having suffered from abuse and neglect is followed by a number of clinical examples illustrating AAT. PMID:18411863

  16. 9 CFR 94.7 - Disposal of animals, meats, and other articles ineligible for importation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ANIMAL PRODUCTS RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE SPONGIFORM ENCEPHALOPATHY: PROHIBITED AND...) Ruminants and swine, and fresh (chilled or frozen) meats, prohibited importation under §§ 94.1, 94.8,...

  17. 9 CFR 94.7 - Disposal of animals, meats, and other articles ineligible for importation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ANIMAL PRODUCTS RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE SPONGIFORM ENCEPHALOPATHY: PROHIBITED AND...) Ruminants and swine, and fresh (chilled or frozen) meats, prohibited importation under §§ 94.1, 94.8,...

  18. 9 CFR 94.7 - Disposal of animals, meats, and other articles ineligible for importation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ANIMAL PRODUCTS RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE SPONGIFORM ENCEPHALOPATHY: PROHIBITED AND...) Ruminants and swine, and fresh (chilled or frozen) meats, prohibited importation under §§ 94.1, 94.8,...

  19. 9 CFR 94.7 - Disposal of animals, meats, and other articles ineligible for importation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ANIMAL PRODUCTS RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE SPONGIFORM ENCEPHALOPATHY: PROHIBITED AND...) Ruminants and swine, and fresh (chilled or frozen) meats, prohibited importation under §§ 94.1, 94.8,...

  20. Clinical features in prion protein-deficient and wild-type cattle inoculated with transmissible mink encephalopathy (TME)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Transmissible spongiform encephalopathies (TSEs) or prion diseases are caused by the propagation of a misfolded form (PrP**d) of the normal cellular prion protein, PrP**c. Recently, we have reported the generation and characterization of PrP**C-deficient cattle (PrP-/-) produced by a seq...

  1. Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles

    PubMed Central

    Johnson, Christopher J; Pedersen, Joel A; Chappell, Rick J; McKenzie, Debbie; Aiken, Judd M

    2007-01-01

    Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite (Mte) retain infectivity following intracerebral inoculation. Here, we assess the oral infectivity of Mte- and soil-bound prions. We establish that prions bound to Mte are orally bioavailable, and that, unexpectedly, binding to Mte significantly enhances disease penetrance and reduces the incubation period relative to unbound agent. Cox proportional hazards modeling revealed that across the doses of TSE agent tested, Mte increased the effective infectious titer by a factor of 680 relative to unbound agent. Oral exposure to Mte-associated prions led to TSE development in experimental animals even at doses too low to produce clinical symptoms in the absence of the mineral. We tested the oral infectivity of prions bound to three whole soils differing in texture, mineralogy, and organic carbon content and found soil-bound prions to be orally infectious. Two of the three soils increased oral transmission of disease, and the infectivity of agent bound to the third organic carbon-rich soil was equivalent to that of unbound agent. Enhanced transmissibility of soil-bound prions may explain the environmental spread of some TSEs despite the presumably low levels shed into the environment. Association of prions with inorganic microparticles represents a novel means by which their oral transmission is enhanced relative to unbound agent. PMID:17616973

  2. 9 CFR 94.18 - Restrictions on importation of meat and edible products from ruminants due to bovine spongiform...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...: For Federal Register citations affecting § 94.18, see the List of CFR Sections Affected, which appears... DISEASE, NEWCASTLE DISEASE, HIGHLY PATHOGENIC AVIAN INFLUENZA, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE SPONGIFORM ENCEPHALOPATHY: PROHIBITED AND RESTRICTED...

  3. Detection of PrP(Sc) in peripheral tissues of clinically affected cattle after oral challenge with bovine spongiform encephalopathy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease that affects cattle and can be transmitted to human beings as new variant Creutzfeldt-Jakob disease (vCJD). A protease-resistant, disease-associated isoform of the prion protein (PrP**Sc) accumulates in the central ner...

  4. Decontamination studies with the agents of bovine spongiform encephalopathy and scrapie.

    PubMed

    Taylor, D M; Fraser, H; McConnell, I; Brown, D A; Brown, K L; Lamza, K A; Smith, G R

    1994-01-01

    Macerates of bovine brain infected with bovine spongiform encephalopathy (BSE) agent, and rodent brain infected with the 263K or ME7 strains of scrapie agent, were subjected to porous-load autoclaving at temperatures between 134 and 138 degrees C for < or = 60 min. Bioassay in rodents showed that none of the regimens produced complete inactivation. Homogenates of BSE-infected bovine brain were exposed for < or = 120 min to solutions of sodium hypochlorite or sodium dichloroisocyanurate containing < or = 16,500 ppm available chlorine. There was no detectable survival of infectivity after the hypochlorite treatments but none of the dichloroisocyanurate solutions produced complete inactivation. Homogenates of BSE-infected bovine brain, and rodent brain infected with the 263K and ME7 strains of scrapie agent, were exposed for < or = 120 min to 1M or 2M sodium hydroxide but no procedure produced complete inactivation of all agents tested. PMID:7832638

  5. The Development of Novel Recombinant Human Gelatins as Replacements for Animal-Derived Gelatin in Pharmaceutical Applications

    NASA Astrophysics Data System (ADS)

    Olsen, David; Chang, Robert; Williams, Kim E.; Polarek, James W.

    We have developed a recombinant expression system to produce a series of novel recombinant human gelatins that can substitute for animal sourced gelatin preparations currently used in pharmaceutical and nutraceutical applications. This system allows the production of human sequence gelatins, or, if desired, gelatins from any other species depending on the availability of the cloned gene. The gelatins produced with this recombinant system are of defined molecular weight, unlike the animal-sourced gelatins, which consist of numerous polypeptides of varying size. The fermentation and purification process used to prepare these recombinant gelatins does not use any human- or animal-derived components and thus this recombinant material should be free from viruses and agents that cause transmissible spongiform encephalopathies. The recombinant gelatins exhibit lot-to-lot reproducibility and we have performed extensive analytical testing on them. We have demonstrated the utility of these novel gelatins as biological stabilizers and plasma expanders, and we have shown they possess qualities that are important in applications where gel formation is critical. Finally, we provide examples of how our system allows the engineering of these recombinant gelatins to optimize the production process.

  6. Postinhibitory rebound neurons and networks are disrupted in retrovirus-induced spongiform neurodegeneration.

    PubMed

    Li, Ying; Davey, Robert A; Sivaramakrishnan, Shobhana; Lynch, William P

    2014-08-01

    Certain retroviruses induce progressive spongiform motor neuron disease with features resembling prion diseases and amyotrophic lateral sclerosis. With the neurovirulent murine leukemia virus (MLV) FrCasE, Env protein expression within glia leads to postsynaptic vacuolation, cellular effacement, and neuronal loss in the absence of neuroinflammation. To understand the physiological changes associated with MLV-induced spongiosis, and its neuronal specificity, we employed patch-clamp recordings and voltage-sensitive dye imaging in brain slices of the mouse inferior colliculus (IC), a midbrain nucleus that undergoes extensive spongiosis. IC neurons characterized by postinhibitory rebound firing (PIR) were selectively affected in FrCasE-infected mice. Coincident with Env expression in microglia and in glia characterized by NG2 proteoglycan expression (NG2 cells), rebound neurons (RNs) lost PIR, became hyperexcitable, and were reduced in number. PIR loss and hyperexcitability were reversed by raising internal calcium buffer concentrations in RNs. PIR-initiated rhythmic circuits were disrupted, and spontaneous synchronized bursting and prolonged depolarizations were widespread. Other IC neuron cell types and circuits within the same degenerative environment were unaffected. Antagonists of NMDA and/or AMPA receptors reduced burst firing in the IC but did not affect prolonged depolarizations. Antagonists of L-type calcium channels abolished both bursts and slow depolarizations. IC infection by the nonneurovirulent isogenic virus Friend 57E (Fr57E), whose Env protein is structurally similar to FrCasE, showed no RN hyperactivity or cell loss; however, PIR latency increased. These findings suggest that spongiform neurodegeneration arises from the unique excitability of RNs, their local regulation by glia, and the disruption of this relationship by glial expression of abnormal protein. PMID:25252336

  7. Postinhibitory rebound neurons and networks are disrupted in retrovirus-induced spongiform neurodegeneration

    PubMed Central

    Li, Ying; Davey, Robert A.; Lynch, William P.

    2014-01-01

    Certain retroviruses induce progressive spongiform motor neuron disease with features resembling prion diseases and amyotrophic lateral sclerosis. With the neurovirulent murine leukemia virus (MLV) FrCasE, Env protein expression within glia leads to postsynaptic vacuolation, cellular effacement, and neuronal loss in the absence of neuroinflammation. To understand the physiological changes associated with MLV-induced spongiosis, and its neuronal specificity, we employed patch-clamp recordings and voltage-sensitive dye imaging in brain slices of the mouse inferior colliculus (IC), a midbrain nucleus that undergoes extensive spongiosis. IC neurons characterized by postinhibitory rebound firing (PIR) were selectively affected in FrCasE-infected mice. Coincident with Env expression in microglia and in glia characterized by NG2 proteoglycan expression (NG2 cells), rebound neurons (RNs) lost PIR, became hyperexcitable, and were reduced in number. PIR loss and hyperexcitability were reversed by raising internal calcium buffer concentrations in RNs. PIR-initiated rhythmic circuits were disrupted, and spontaneous synchronized bursting and prolonged depolarizations were widespread. Other IC neuron cell types and circuits within the same degenerative environment were unaffected. Antagonists of NMDA and/or AMPA receptors reduced burst firing in the IC but did not affect prolonged depolarizations. Antagonists of L-type calcium channels abolished both bursts and slow depolarizations. IC infection by the nonneurovirulent isogenic virus Friend 57E (Fr57E), whose Env protein is structurally similar to FrCasE, showed no RN hyperactivity or cell loss; however, PIR latency increased. These findings suggest that spongiform neurodegeneration arises from the unique excitability of RNs, their local regulation by glia, and the disruption of this relationship by glial expression of abnormal protein. PMID:25252336

  8. Transmission of chronic wasting disease in Wisconsin white-tailed deer: implications for disease spread and management.

    PubMed

    Jennelle, Christopher S; Henaux, Viviane; Wasserberg, Gideon; Thiagarajan, Bala; Rolley, Robert E; Samuel, Michael D

    2014-01-01

    Few studies have evaluated the rate of infection or mode of transmission for wildlife diseases, and the implications of alternative management strategies. We used hunter harvest data from 2002 to 2013 to investigate chronic wasting disease (CWD) infection rate and transmission modes, and address how alternative management approaches affect disease dynamics in a Wisconsin white-tailed deer population. Uncertainty regarding demographic impacts of CWD on cervid populations, human and domestic animal health concerns, and potential economic consequences underscore the need for strategies to control CWD distribution and prevalence. Using maximum-likelihood methods to evaluate alternative multi-state deterministic models of CWD transmission, harvest data strongly supports a frequency-dependent transmission structure with sex-specific infection rates that are two times higher in males than females. As transmissible spongiform encephalopathies are an important and difficult-to-study class of diseases with major economic and ecological implications, our work supports the hypothesis of frequency-dependent transmission in wild deer at a broad spatial scale and indicates that effective harvest management can be implemented to control CWD prevalence. Specifically, we show that harvest focused on the greater-affected sex (males) can result in stable population dynamics and control of CWD within the next 50 years, given the constraints of the model. We also provide a quantitative estimate of geographic disease spread in southern Wisconsin, validating qualitative assessments that CWD spreads relatively slowly. Given increased discovery and distribution of CWD throughout North America, insights from our study are valuable to management agencies and to the general public concerned about the impacts of CWD on white-tailed deer populations. PMID:24658535

  9. Transmission of Chronic Wasting Disease in Wisconsin White-Tailed Deer: Implications for Disease Spread and Management

    PubMed Central

    Jennelle, Christopher S.; Henaux, Viviane; Wasserberg, Gideon; Thiagarajan, Bala; Rolley, Robert E.; Samuel, Michael D.

    2014-01-01

    Few studies have evaluated the rate of infection or mode of transmission for wildlife diseases, and the implications of alternative management strategies. We used hunter harvest data from 2002 to 2013 to investigate chronic wasting disease (CWD) infection rate and transmission modes, and address how alternative management approaches affect disease dynamics in a Wisconsin white-tailed deer population. Uncertainty regarding demographic impacts of CWD on cervid populations, human and domestic animal health concerns, and potential economic consequences underscore the need for strategies to control CWD distribution and prevalence. Using maximum-likelihood methods to evaluate alternative multi-state deterministic models of CWD transmission, harvest data strongly supports a frequency-dependent transmission structure with sex-specific infection rates that are two times higher in males than females. As transmissible spongiform encephalopathies are an important and difficult-to-study class of diseases with major economic and ecological implications, our work supports the hypothesis of frequency-dependent transmission in wild deer at a broad spatial scale and indicates that effective harvest management can be implemented to control CWD prevalence. Specifically, we show that harvest focused on the greater-affected sex (males) can result in stable population dynamics and control of CWD within the next 50 years, given the constraints of the model. We also provide a quantitative estimate of geographic disease spread in southern Wisconsin, validating qualitative assessments that CWD spreads relatively slowly. Given increased discovery and distribution of CWD throughout North America, insights from our study are valuable to management agencies and to the general public concerned about the impacts of CWD on white-tailed deer populations. PMID:24658535

  10. Molecular Modeling of Prion Transmission to Humans

    PubMed Central

    Levavasseur, Etienne; Privat, Nicolas; Martin, Juan-Carlos Espinosa; Simoneau, Steve; Baron, Thierry; Flan, Benoit; Torres, Juan-Maria; Haïk, Stéphane

    2014-01-01

    Using different prion strains, such as the variant Creutzfeldt-Jakob disease agent and the atypical bovine spongiform encephalopathy agents, and using transgenic mice expressing human or bovine prion protein, we assessed the reliability of protein misfolding cyclic amplification (PMCA) to model interspecies and genetic barriers to prion transmission. We compared our PMCA results with in vivo transmission data characterized by attack rates, i.e., the percentage of inoculated mice that developed the disease. Using 19 seed/substrate combinations, we observed that a significant PMCA amplification was only obtained when the mouse line used as substrate is susceptible to the corresponding strain. Our results suggest that PMCA provides a useful tool to study genetic barriers to transmission and to study the zoonotic potential of emerging prion strains. PMID:25279820