Science.gov

Sample records for animal transmissible spongiform

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

    USDA-ARS?s Scientific Manuscript database

    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. Failure to demonstrate involvement of antibodies to Acinetobacter calcoaceticus in transmissible spongiform encephalopathies of animals.

    PubMed

    Nielsen, K; Widdison, J; Balachandran, A; Stevenson, D; Algire, J

    2002-10-28

    Acinetobacter calcoaceticus, a soil microbe, contains molecular sequences which resemble those found in neurofilaments of the brain tissue. It was hypothesized that if cattle ingest large amounts of feedstuff containing A. calcoaceticus, they may develop an autoimmune reaction, with consequences of pathological changes associated with transmissible spongiform encephalopathies (TSEs). The hypothesis was tested using a small number of serum samples collected from cattle and it was found that affected individuals had elevated serum antibody levels to this organism. If this finding was substantiated, it would provide a possible means of diagnosing TSEs in vivo. In the present communication, a larger number of cattle, elk and sheep with or without TSEs were tested using A. calcoaceticus whole cell and lipopolysaccharide antigens as well as myelin basic protein (MBP). It was found that antibody levels in normal and affected animals overlapped considerably, thus casting doubt on the usefulness of these antigens as diagnostic tools for TSEs and on the hypothesis of A. calcoaceticus being a cause of TSEs.

  3. 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

  4. 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.

  5. The transmissible spongiform encephalopathies of livestock

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  7. 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".

  8. Cell culture models of transmissible spongiform encephalopathies.

    PubMed

    Béranger, F; Mangé, A; Solassol, J; Lehmann, S

    2001-11-30

    In this review, we describe the generation and use of cell culture models of transmissible spongiform encephalopathies, also known as prion diseases. These models include chronically prion-infected cell lines, as well as cultures expressing variable amounts of wild-type, mutated, or chimeric prion proteins. These cell lines have been widely used to investigate the biology of both the normal and the pathological isoform of the prion protein. They have also contributed to the comprehension of the pathogenic processes occurring in transmissible spongiform encephalopathies and in the development of new therapeutic approaches of these diseases.

  9. Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle: comparison to bovine spongiform encephalopathy in cattle.

    PubMed

    Hamir, Amir N; Kehrli, Marcus E; Kunkle, Robert A; Greenlee, Justin J; Nicholson, Eric M; Richt, Jürgen A; Miller, Janice M; Cutlip, Randall C

    2011-05-01

    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. The emergence of BSE and its spread to human beings in the form of variant Creutzfeldt-Jakob disease (vCJD) resulted in interest in susceptibility of cattle to CWD, TME and scrapie. Experimental cross-species transmission of TSE agents provides valuable information for potential host ranges of known TSEs. Some interspecies transmission studies have been conducted by inoculating disease-causing prions intracerebrally (IC) rather than orally; the latter is generally effective in intraspecies transmission studies and is considered a natural route by which animals acquire TSEs. The "species barrier" concept for TSEs resulted from unsuccessful interspecies oral transmission attempts. Oral inoculation of prions mimics the natural disease pathogenesis route whereas IC inoculation is rather artificial; however, it is very efficient since it requires smaller dosage of inoculum, and typically results in higher attack rates and reduces incubation time compared to oral transmission. A species resistant to a TSE by IC inoculation would have negligible potential for successful oral transmission. To date, results indicate that cattle are susceptible to IC inoculation of scrapie, TME, and CWD but it is only when inoculated with TME do they develop spongiform lesions or clinical disease similar to BSE. Importantly, cattle are resistant to oral transmission of scrapie or CWD; susceptibility of cattle to oral transmission of TME is not yet determined. © 2011 The Author(s)

  10. 76 FR 38667 - Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-01

    ... HUMAN SERVICES Food and Drug Administration Transmissible Spongiform Encephalopathies Advisory Committee... be open to the public. Name of Committee: Transmissible Spongiform Encephalopathies Advisory... available at the following link. Transmissible Spongiform Encephalopathies Advisory Committee http://fda...

  11. Public health issues and clinical and neurological characteristics of the new variant of Creutzfeldt-Jakob disease and other human and animal transmissible spongiform encephalopathies: memorandum from two WHO meetings.

    PubMed Central

    1996-01-01

    The transmissible spongiform encephalopathies (TSEs) include bovine spongiform encephalopathy (BSE), which was first described in 1986 in cattle in the United Kingdom, but has occurred subsequently also in other countries, and Creutzfeldt-Jakob disease (CJD) in humans, which is rare but with a worldwide distribution. Recently a new variant form of CJD, with a characteristic clinical and pathological phenotype, has been identified in the United Kingdom in a series of 11 young patients. This Memorandum reports the findings of two WHO Consultations. The first, held on 2-3 April 1996, issued conclusions and recommendations on certain animal products in order to protect the health of consumers. The second, held on 14-16 May 1996, examined, inter alia, the findings associated with the new variant of CJD, compared these findings with those for other TSEs, and proposed a protocol for the diagnosis and surveillance of CJD and related diseases. PMID:9002325

  12. 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

    2016-01-07

    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.

  13. Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle

    PubMed Central

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

    2017-01-01

    To determine oral transmissibility of the L-type bovine spongiform encephalopathy (BSE) prion, we orally inoculated 16 calves with brain homogenates of the agent. Only 1 animal, given a high dose, showed signs and died at 88 months. These results suggest low risk for oral transmission of the L-BSE agent among cattle. PMID:28098532

  14. Oral Transmission of L-Type Bovine Spongiform Encephalopathy Agent among Cattle.

    PubMed

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

    2017-02-01

    To determine oral transmissibility of the L-type bovine spongiform encephalopathy (BSE) prion, we orally inoculated 16 calves with brain homogenates of the agent. Only 1 animal, given a high dose, showed signs and died at 88 months. These results suggest low risk for oral transmission of the L-BSE agent among cattle.

  15. 78 FR 11207 - Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-15

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Transmissible Spongiform Encephalopathies Advisory Committee... be open to the public. Name of Committee: Transmissible Spongiform Encephalopathies Advisory...

  16. Risk management of transmissible spongiform encephalopathies in Europe.

    PubMed

    Heim, D; Kihm, U

    2003-04-01

    Bovine spongiform encephalopathy (BSE) was first described in the United Kingdom (UK) in November 1986. After the introduction of an active surveillance system, most countries in Europe have reported BSE cases in the cattle population. This indicates that the use of active surveillance in addition to passive surveillance is important to assess the true BSE status in a country. Scrapie, a transmissible spongiform encephalopathy (TSE) in sheep and goats, has been reported in countries throughout the world with a few notable exceptions. Concern was expressed that BSE could have been introduced into sheep and goats. Currently, distinguishing between scrapie and BSE in small ruminants is only possible through lengthy experiments in mice. Preliminary results of active surveillance, introduced in 2002, show that significant under-reporting occurred. The history of BSE in cattle shows that risk assessments concerning the risk in a given country were often ignored and subsequent risk management decisions were inaccurate, i.e. although the risk was probable, no measures were taken in terms of either animal or human health. Furthermore, the effect of the measures taken was often overestimated and these had to be amended several times. The most important action to prevent new cases of TSEs occurring is by banning the feeding meat-and-bone meal (MBM) to ruminants. Further measures to be considered are the exclusion of specified risk material and carcasses from rendering, the process parameters for rendering of animal waste and the prevention of cross-contamination of feed with MBM. The most important measures to protect the consumer are the ban on specified risk material, such as brain and spinal cord, which may contain particularly high concentrations of the BSE agent, and the ban on mechanically recovered meat. The most important measures taken in Europe and the scientific background thereof are described and discussed.

  17. Prions and the human transmissible spongiform encephalopathies.

    PubMed

    Scully, Crispian; Smith, Andrew J; Bagg, Jeremy

    2003-07-01

    The last 5 years have seen the emergence of a new disease in humans (vCJD), mainly in the United Kingdom. This emergence has been accompanied by an explosion of scientific data on a novel group of the responsible infectious agents called prions and has profound implications for infection control and transfusion policies. Also of concern is the finding of prions in neural, gingival, pulpal, and salivary tissue in animal models and significant titers of infectivity from extraneural organs (particularly, in cases of vCJD, in lymphoreticular tissues). There is limited information on the presence of prion proteins in the oral tissues from human studies. Because of the differences in patterns of disease in animal models and in strains of prion protein, it is difficult to extrapolate directly these findings to humans, but it illustrates a potential for transmission by way of the dental route. High levels of infectivity may be present in tissues early in the incubation period and before clinical signs and symptoms. The dental profession must turn its attention to the routine decontamination of dental instruments to ensure that these procedures are performed to the highest regulatory standard. Clinicians and manufacturers must work closely together to develop instruments that are either single use or can be presented in a form that can be more easily decontaminated. Clinicians must pay close attention to manufacturers' decontamination instructions and must not reuse items designated as single use, such as endodontic files. Improvements in compliance with these requirements will not only reduce the risk of transmission of TSEs but also other less tenacious infectious agents.

  18. Comparison of Abnormal Prion Protein Glycoform Patterns from Transmissible Spongiform Encephalopathy Agent-Infected Deer, Elk, Sheep, and Cattle

    PubMed Central

    Race, Richard E.; Raines, Anne; Baron, Thierry G. M.; Miller, Michael W.; Jenny, Allen; Williams, Elizabeth S.

    2002-01-01

    Analysis of abnormal prion protein glycoform patterns from chronic wasting disease (CWD)-affected deer and elk, scrapie-affected sheep and cattle, and cattle with bovine spongiform encephalopathy failed to identify patterns capable of reliably distinguishing these transmissible spongiform encephalopathy diseases. However, PrP-res patterns sometimes differed among individual animals, suggesting infection by different or multiple CWD strains in some species. PMID:12414979

  19. 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

  20. The human transmissible spongiform encephalopathies (TSEs): implications for dental practitioners.

    PubMed

    Porter, S; Scully, C; Ridgway, G L; Bell, J

    2000-04-22

    Transmissible spongiform encephalopathies (TSEs) are rare, fatal degenerative brain diseases which affect humans and certain animals, and are caused by inheritance or acquisition of prions (PrPs). Inherited TSEs include Fatal Familial Insomnia (FFI), Gerstmann-Straussler-Scheinker syndrome (GSS) and other less well clinically characterised disorders, while the human infective TSEs include sporadic, iatrogenic and variant Creutzfeldt-Jakob disease (vCJD). The causative prions are found especially in neural tissues and spinal fluid, and in the case of vCJD, in lymphoreticular tissue. Available epidemiological evidence suggests that normal social or routine clinical contact with affected patients does not present a risk to health care workers, relatives or the community. Isolation of patients is not considered necessary. Nevertheless as the prions are resistant to conventional chemical, irradiation and heat sterilisation methods, highly specific cross-infection control measures are required for the dental management of patients with, or at notable risk, of TSE. The present article reviews current knowledge of the clinical consequences of prion disease and provides information regarding necessary changes to the cross-infection routine when managing patients infected, or at risk of, prion disease.

  1. Bovine Spongiform Encephalopathy

    USDA-ARS?s Scientific Manuscript database

    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...

  2. Risk management of the transmissible spongiform encephalopathies in North America.

    PubMed

    Kellar, J A; Lees, V W

    2003-04-01

    As North American Free Trade Agreement partners, Canada, the United States of America (USA) and Mexico apply independent but harmonised transmissible spongiform encephalopathy (TSE) risk management strategies in observance of Office International des Epizooties guidelines. The divergence between bovine spongiform encephalopathy (BSE) risk management approaches in North American and Europe reflects comparatively reduced external and internal BSE risks in North America. The external quarantine and internal surveillance measures adopted for BSE respond to several iterations of national risk assessments initiated in the early 1990s and revised as recently as 2002. Feed bans applied since 1997 to preclude establishment of BSE also bear the potential to limit intra-species and inter-species exposure to scrapie, chronic wasting disease (CWD) and transmissible mink encephalopathy (TME). Surveillance continues for the four TSEs through collaborative efforts of national and sub-national veterinary infrastructures and accompanying laboratory networks. Mexico has never identified the presence of any TSE. The last diagnosed case of TME in North America dates back to 1985. Since the only recognised appearance in Canada through an import from Great Britain in 1993, BSE has not been detected in North America. Scrapie and CWD remain at generally low prevalence in Canada and the USA. Independent but harmonised eradication programmes target elimination of the latter two diseases.

  3. 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.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  5. The transmissible spongiform encephalopathies (prion diseases): a review for dental surgeons.

    PubMed

    Gill, D S; Tredwin, C J; Gill, S K; Ironside, J W

    2001-12-01

    The transmissible spongiform encephalopathies (prion diseases) are a fatal group of neurological diseases characterised by the accumulation of an abnormal form of prion protein in the brain. In humans, these disorders occur in sporadic, acquired and familial forms. Outbreaks of bovine spongiform encephalopathy, predominantly in the United Kingdom, and the emergence of a clinically and pathologically distinct human prion disease, variant CJD, has generated much interest in the transmissible spongiform encephalopathies. As the agent is detectable in lymphoid and neural tissue in variant CJD, clinicians should be aware of the possibility of cross infection of the causative agent. This is particularly important because the abnormal prion protein is resistant to routine sterilisation procedures. This article reviews the transmissible spongiform encephalopathies, and summarises guidelines concerning prevention of crossinfection when treating patients with or at risk of developing prion disease.

  6. A Heparin Purification Process Removes Spiked Transmissible Spongiform Encephalopathy Agent.

    PubMed

    Bett, Cyrus; Grgac, Ksenija; Long, Dianna; Karfunkle, Michael; Keire, David A; Asher, David M; Gregori, Luisa

    2017-01-23

    In 2000, bovine heparin was withdrawn from the US market for fear of contamination with bovine spongiform encephalopathy (BSE) agent, the cause of variant Creutzfeldt-Jakob disease in humans. Thus, US heparin is currently sourced only from pig intestines. Availability of alternative sources of crude heparin, a life-saving drug, would benefit public health. Bovine heparin is an obvious option, but BSE clearance by the bovine heparin manufacturing process should be evaluated. To this end, using hamster 263K scrapie as a surrogate for BSE agent, we applied a four-step bench-scale heparin purification protocol resembling a typical heparin manufacturing process to investigate removal of the spiked scrapie agent. We removed aliquots from each step and analyzed them for residual abnormal prion protein (PrP(TSE)) using a sensitive in vitro method, real-time quaking-induced conversion (RT-QuIC) assay, and for infectivity using animal bioassays. The purification process reduced infectivity by 3.6 log10 and removed PrP(TSE), measured as seeding activity, by 3.4 log10. NaOH treatment was the most effective removal step tested. We also investigated NaOH at different concentrations and pH: the results showed that as much as 5.2 log10 of PrP(TSE) seeding activity was removed at pH 12.5. Thus, changes to the concentration, treatment time, and temperature of alkaline extraction might further improve removal. Our results, using a basic heparin manufacturing process, inform efforts to reintroduce safe bovine heparin in the USA.

  7. Classical Bovine Spongiform Encephalopathy by Transmission of H-Type Prion in Homologous Prion Protein Context

    PubMed Central

    Andréoletti, Olivier; Lacroux, Caroline; Prieto, Irene; Lorenzo, Patricia; Larska, Magdalena; Baron, Thierry; Espinosa, Juan-Carlos

    2011-01-01

    Bovine spongiform encephalopathy (BSE) and BSE-related disorders have been associated with a single major prion strain. Recently, 2 atypical, presumably sporadic forms of BSE have been associated with 2 distinct prion strains that are characterized mainly by distinct Western blot profiles of abnormal protease-resistant prion protein (PrPres), named high-type (BSE-H) and low-type (BSE-L), that also differed from classical BSE. We characterized 5 atypical BSE-H isolates by analyzing their molecular and neuropathologic properties during transmission in transgenic mice expressing homologous bovine prion protein. Unexpectedly, in several inoculated animals, strain features emerged that were highly similar to those of classical BSE agent. These findings demonstrate the capability of an atypical bovine prion to acquire classical BSE–like properties during propagation in a homologous bovine prion protein context and support the view that the epidemic BSE agent could have originated from such a cattle prion. PMID:21888788

  8. Use of murine bioassay to resolve ovine transmissible spongiform encephalopathy cases showing a bovine spongiform encephalopathy molecular profile.

    PubMed

    Beck, Katy E; Sallis, Rosemary E; Lockey, Richard; Vickery, Christopher M; Béringue, Vincent; Laude, Hubert; Holder, Thomas M; Thorne, Leigh; Terry, Linda A; Tout, Anna C; Jayasena, Dhanushka; Griffiths, Peter C; Cawthraw, Saira; Ellis, Richard; Balkema-Buschmann, Anne; Groschup, Martin H; Simmons, Marion M; Spiropoulos, John

    2012-05-01

    Two cases of unusual transmissible spongiform encephalopathy (TSE) were diagnosed on the same farm in ARQ/ARQ PrP sheep showing attributes of both bovine spongiform encephalopathy (BSE) and scrapie. These cases, UK-1 and UK-2, were investigated further by transmissions to wild-type and ovine transgenic mice. Lesion profiles (LP) on primary isolation and subpassage, incubation period (IP) of disease, PrP(Sc) immunohistochemical (IHC) deposition pattern and Western blot profiles were used to characterize the prions causing disease in these sheep. Results showed that both cases were compatible with scrapie. The presence of BSE was contraindicated by the following: LP on primary isolation in RIII and/or MR (modified RIII) mice; IP and LP after serial passage in wild-type mice; PrP(Sc) deposition pattern in wild-type mice; and IP and Western blot data in transgenic mice. Furthermore, immunohistochemistry (IHC) revealed that each case generated two distinct PrP(Sc) deposition patterns in both wild-type and transgenic mice, suggesting that two scrapie strains coexisted in the ovine hosts. Critically, these data confirmed the original differential IHC categorization that these UK-1 and UK-2 cases were not compatible with BSE.

  9. Bovine Spongiform Encephalopathy: Atypical Pros and Cons

    USDA-ARS?s Scientific Manuscript database

    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...

  10. 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.

  11. Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay

    PubMed Central

    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

  12. 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

    2015-03-10

    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.

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  15. Nonenzymatic glycation at the N terminus of pathogenic prion protein in transmissible spongiform encephalopathies.

    PubMed

    Choi, Yeong-Gon; Kim, Jae-Il; Jeon, Yong-Chul; Park, Seok-Joo; Choi, Eun-Kyoung; Rubenstein, Richard; Kascsak, Richard J; Carp, Richard I; Kim, Yong-Sun

    2004-07-16

    Transmissible spongiform encephalopathies (TSEs) are transmissible neurodegenerative diseases characterized by the accumulation of an abnormally folded prion protein, termed PrPSc, and the development of pathological features of astrogliosis, vacuolation, neuronal cell loss, and in some cases amyloid plaques. Although considerable structural characterization of prion protein has been reported, neither the method of conversion of cellular prion protein, PrPC, into the pathogenic isoform nor the post-translational modification processes involved is known. We report that in animal and human TSEs, one or more lysines at residues 23, 24, and 27 of PrPSc are covalently modified with advanced glycosylation end products (AGEs), which may be carboxymethyl-lysine (CML), one of the structural varieties of AGEs. The arginine residue at position 37 may also be modified with AGE, but not the arginine residue at position 25. This result suggests that nonenzymatic glycation is one of the post-translational modifications of PrP(Sc). Furthermore, immunostaining studies indicate that, at least in clinically affected hamsters, astrocytes are the first site of this glycation process.

  16. Foodborne Transmission of Bovine Spongiform Encephalopathy to Nonhuman Primates

    PubMed Central

    Yutzy, Barbara; Schulz-Schaeffer, Walter; Kruip, Carina; Hahmann, Uwe; Bierke, Pär; Torres, Juan-Maria; Kim, Yong-Sun; Thomzig, Achim; Beekes, Michael; Hunsmann, Gerhard; Loewer, Johannes

    2013-01-01

    Risk for human exposure to bovine spongiform encephalopathy (BSE)–inducing agent was estimated in a nonhuman primate model. To determine attack rates, incubation times, and molecular signatures, we orally exposed 18 macaques to 1 high dose of brain material from cattle with BSE. Several macaques were euthanized at regular intervals starting at 1 year postinoculation, and others were observed until clinical signs developed. Among those who received ≥5 g BSE-inducing agent, attack rates were 100% and prions could be detected in peripheral tissues from 1 year postinoculation onward. The overall median incubation time was 4.6 years (3.7–5.3). However, for 3 macaques orally exposed on multiple occasions, incubation periods were at least 7–10 years. Before clinical signs were noted, we detected a non-type 2B signature, indicating the existence of atypical prion protein during the incubation period. This finding could affect diagnosis of variant Creutzfeldt-Jakob disease in humans and might be relevant for retrospective studies of positive tonsillectomy or appendectomy specimens because time of infection is unknown. PMID:23647575

  17. Foodborne transmission of bovine spongiform encephalopathy to nonhuman primates.

    PubMed

    Holznagel, Edgar; Yutzy, Barbara; Schulz-Schaeffer, Walter; Kruip, Carina; Hahmann, Uwe; Bierke, Pär; Torres, Juan-Maria; Kim, Yong-Sun; Thomzig, Achim; Beekes, Michael; Hunsmann, Gerhard; Loewer, Johannes

    2013-05-01

    Risk for human exposure to bovine spongiform encephalopathy (BSE)-inducing agent was estimated in a nonhuman primate model. To determine attack rates, incubation times, and molecular signatures, we orally exposed 18 macaques to 1 high dose of brain material from cattle with BSE. Several macaques were euthanized at regular intervals starting at 1 year postinoculation, and others were observed until clinical signs developed. Among those who received ≥5 g BSE-inducing agent, attack rates were 100% and prions could be detected in peripheral tissues from 1 year postinoculation onward. The overall median incubation time was 4.6 years (3.7-5.3). However, for 3 macaques orally exposed on multiple occasions, incubation periods were at least 7-10 years. Before clinical signs were noted, we detected a non-type 2B signature, indicating the existence of atypical prion protein during the incubation period. This finding could affect diagnosis of variant Creutzfeldt-Jakob disease in humans and might be relevant for retrospective studies of positive tonsillectomy or appendectomy specimens because time of infection is unknown.

  18. Laboratory activities involving transmissible spongiform encephalopathy causing agents: risk assessment and biosafety recommendations in Belgium.

    PubMed

    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.

  19. 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

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

    PubMed Central

    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 (A136R154Q171 genotype). 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 A136R154Q171 genotype 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

  1. The prion diseases of animals

    USDA-ARS?s Scientific Manuscript database

    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...

  2. Possible Case of Maternal Transmission of Feline Spongiform Encephalopathy in a Captive Cheetah

    PubMed Central

    Bencsik, Anna; Debeer, Sabine; Petit, Thierry; Baron, Thierry

    2009-01-01

    Feline spongiform encephalopathy (FSE) is considered to be related to bovine spongiform encephalopathy (BSE) and has been reported in domestic cats as well as in captive wild cats including cheetahs, first in the United Kingdom (UK) and then in other European countries. In France, several cases were described in cheetahs either imported from UK or born in France. Here we report details of two other FSE cases in captive cheetah including a 2nd case of FSE in a cheetah born in France, most likely due to maternal transmission. Complete prion protein immunohistochemical study on both brains and peripheral organs showed the close likeness between the two cases. In addition, transmission studies to the TgOvPrP4 mouse line were also performed, for comparison with the transmission of cattle BSE. The TgOvPrP4 mouse brains infected with cattle BSE and cheetah FSE revealed similar vacuolar lesion profiles, PrPd brain mapping with occurrence of typical florid plaques. Collectively, these data indicate that they harbor the same strain of agent as the cattle BSE agent. This new observation may have some impact on our knowledge of vertical transmission of BSE agent-linked TSEs such as in housecat FSE, or vCJD. PMID:19738899

  3. Identification of a Heritable Polymorphism in Bovine PRNP Associated with Genetic Transmissible Spongiform Encephalopathy: Evidence of Heritable BSE

    PubMed Central

    Richt, Juergen A.; Kehrli, Marcus E.; Greenlee, Justin J.

    2008-01-01

    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 disease phenotype and they have not been linked to the consumption of contaminated feed. Interestingly, the 2006 US H-type atypical BSE animal had a polymorphism at codon 211 of the bovine prion gene resulting in a glutamic acid to lysine substitution (E211K). This substitution is analogous a human polymorphism associated with the most prevalent form of heritable TSE in humans, and it is considered to have caused BSE in the 2006 US atypical BSE animal. In order to determine if this amino acid change is a heritable trait in cattle, we sequenced the prion alleles of the only known offspring of this animal, a 2-year-old heifer. Principal Findings Sequence analysis revealed that both the 2006 US atypical BSE animal and its 2-year-old heifer were heterozygous at bovine prion gene nucleotides 631 through 633 for GAA (glutamic acid) and AAA (lysine). Both animals carry the E211K polymorphism, indicating that the allele is heritable and may persist within the cattle population. Conclusions This is the first evidence that the E211K polymorphism is a germline polymorphism, not a somatic mutation, suggesting BSE may be transmitted genetically in cattle. In the event that E211K proves to result in a genetic form of BSE, this would be the first indication that all 3 etiologic forms of TSEs (spontaneous, hereditary, and infectious) are present in a non-human species. Atypical BSE arising as both genetic and spontaneous disease, in the context of reports that at least some forms of atypical BSE can convert to classical BSE in mice, suggests a cattle origin for classical BSE. PMID:18698343

  4. The early history of the transmissible spongiform encephalopathies exemplified by scrapie.

    PubMed

    Schneider, Kurt; Fangerau, Heiner; Michaelsen, Britta; Raab, Wolfgang H-M

    2008-12-16

    Transmissible spongiform encephalopathies (TSE) is a group of diseases that is unique in comprising disorders that can occur sporadically, are hereditary and/or infectious. The transmissible pathogen--the prion--is distinct from all other pathogens in being devoid of nucleic acids. During the elucidation of these disorders, many different--and contradictory--theories have been put forward. Early researchers, mostly driven by the economic impact of these diseases on sheep farming, engaged in heavy disputes concerning heredity vs. infectivity of scrapie. Following the experimental demonstration of scrapie's infectivity during the 20th century, research focused on the characterization of the nature of the transmissible agent. The current work comprehensively summarizes the available early literature on TSE research. A review of the historical literature is presented, describing the efforts in breeding, transmission experiments, and theories about the nature of the infectious agent.

  5. Monitoring of clinical signs in goats with transmissible spongiform encephalopathies

    PubMed Central

    2010-01-01

    Background As there is limited information about the clinical signs of BSE and scrapie in goats, studies were conducted to describe the clinical progression of scrapie and BSE in goats and to evaluate a short clinical protocol for its use in detecting scrapie-affected goats in two herds with previously confirmed scrapie cases. Clinical assessments were carried out in five goats intracerebrally infected with the BSE agent as well as five reported scrapie suspects and 346 goats subject to cull from the two herds, 24 of which were retained for further monitoring. The brain and selected lymphoid tissue were examined by postmortem tests for disease confirmation. Results The sensitivity and specificity of the short clinical protocol in detecting a scrapie case in the scrapie-affected herds was 3.9% and 99.6%, respectively, based on the presence of tremor, positive scratch test, extensive hair loss, ataxia and absent menace response. All BSE- and scrapie-affected goats displayed abnormalities in sensation (over-reactivity to external stimuli, startle responses, pruritus, absent menace response) and movement (ataxia, tremor, postural deficits) at an advanced clinical stage but the first detectable sign associated with scrapie or BSE could vary between animals. Signs of pruritus were not always present despite similar prion protein genotypes. Clinical signs of scrapie were also displayed by two scrapie cases that presented with detectable disease-associated prion protein only in lymphoid tissues. Conclusions BSE and scrapie may present as pruritic and non-pruritic forms in goats. Signs assessed for the clinical diagnosis of scrapie or BSE in goats should include postural and gait abnormalities, pruritus and visual impairment. However, many scrapie cases will be missed if detection is solely based on the display of clinical signs. PrPd accumulation in the brain appeared to be related to the severity of clinical disease but not to the display of individual neurological signs

  6. Foodborne Transmission of Bovine Spongiform Encephalopathy to Non-Human Primates Results in Preclinical Rapid-Onset Obesity

    PubMed Central

    Strom, Alexander; Yutzy, Barbara; Kruip, Carina; Ooms, Mark; Schloot, Nanette C.; Roden, Michael; Scott, Fraser W.; Loewer, Johannes; Holznagel, Edgar

    2014-01-01

    Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE)-infected female cynomolgus monkeys (Macaca fascicularis). The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c.) infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (β = 0.915; P<0.0001) which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity. PMID:25090610

  7. Foodborne transmission of bovine spongiform encephalopathy to non-human primates results in preclinical rapid-onset obesity.

    PubMed

    Strom, Alexander; Yutzy, Barbara; Kruip, Carina; Ooms, Mark; Schloot, Nanette C; Roden, Michael; Scott, Fraser W; Loewer, Johannes; Holznagel, Edgar

    2014-01-01

    Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE)-infected female cynomolgus monkeys (Macaca fascicularis). The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c.) infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (β = 0.915; P<0.0001) which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity.

  8. Vertical Transmission of Bovine Spongiform Encephalopathy Prions Evaluated in a Transgenic Mouse Model

    PubMed Central

    Castilla, J.; Brun, A.; Díaz-San Segundo, F.; Salguero, F. J.; Gutiérrez-Adán, A.; Pintado, B.; Ramírez, M. A.; del Riego, L.; Torres, J. M.

    2005-01-01

    In this work we show evidence of mother-to-offspring transmission in a transgenic mouse line expressing bovine PrP (boTg) experimentally infected by intracerebral administration of bovine spongiform encephalopathy (BSE) prions. PrPres was detected in brains of newborns from infected mothers only when mating was allowed near to the clinical stage of disease, when brain PrPres deposition could be detected by Western blot analysis. Attempts to detect infectivity in milk after intracerebral inoculation in boTg mice were unsuccessful, suggesting the involvement of other tissues as carriers of prion dissemination. The results shown here prove the ability of BSE prions to spread centrifugally from the central nervous system to peripheral tissues and to offspring in a mouse model. Also, these results may complement previous epidemiological data supporting the occurrence of vertical BSE transmission in cattle. PMID:15956610

  9. Inactivation of transmissible spongiform encephalopathy agents during the manufacture of dicalcium phosphate from bone.

    PubMed

    Grobben, A H; Steele, P J; Somerville, R A; Taylor, D M

    2006-03-18

    Dicalcium phosphate was prepared from industrial crushed bone artificially contaminated with transmissible spongiform encephalopathy agents in two experiments carried out in an accurately scaled-down laboratory model of the industrial manufacturing process. In one experiment, 10 g of mouse brain infected with the 301V strain of mouse-passaged bovine spongiform encephalopathy agent was added to the crushed bone; in the other experiment, 10 g of hamster brain infected with the 263K strain of hamster-passaged scrapie agent was added. Samples of the infectious brain and dried dicalcium phosphate were assayed for the amount of 301V or 263K infectivity present. The titre of infectivity of the 301V-infected brain was 10(7.7) intracerebral ID50/g; that of the 263K-infected brain was 10(8.0) intracerebral ID50/g. The titres of the dried samples of dicalcium phosphate were 10(2.5) ID50/g in the experiment spiked with 301V and 10(2.7) ID50/g in the experiment spiked with 263K. The calculated clearance factors were 10(3.9) for the experiment with 301V and 10(3.8) for the experiment with 263K.

  10. Dissociation of Prion Protein Amyloid Seeding from Transmission of a Spongiform Encephalopathy

    PubMed Central

    Piccardo, Pedro; King, Declan; Telling, Glenn; Manson, Jean C.

    2013-01-01

    Misfolding and aggregation of proteins are common pathogenic mechanisms of a group of diseases called proteinopathies. The formation and spread of proteinaceous lesions within and between individuals were first described in prion diseases and proposed as the basis of their infectious nature. Recently, a similar “prion-like” mechanism of transmission has been proposed in other neurodegenerative diseases such as Alzheimer's disease. We investigated if misfolding and aggregation of corrupted prion protein (PrPTSE) are always associated with horizontal transmission of disease. Knock-in transgenic mice (101LL) expressing mutant PrP (PrP-101L) that are susceptible to disease but do not develop any spontaneous neurological phenotype were inoculated with (i) brain extracts containing PrPTSE from healthy 101LL mice with PrP plaques in the corpus callosum or (ii) brain extracts from mice overexpressing PrP-101L with neurological disease, severe spongiform encephalopathy, and formation of proteinase K-resistant PrPTSE. In all instances, 101LL mice developed PrP plaques in the area of inoculation and vicinity in the absence of clinical disease or spongiform degeneration of the brain. Importantly, 101LL mice did not transmit disease on serial passage, ruling out the presence of subclinical infection. Thus, in both experimental models the formation of PrPTSE is not infectious. These results have implications for the interpretation of tests based on the detection of protein aggregates and suggest that de novo formation of PrPTSE in the host does not always result in a transmissible prion disease. In addition, these results question the validity of assuming that all diseases due to protein misfolding can be transmitted between individuals. PMID:24027305

  11. The clearance of viruses and transmissible spongiform encephalopathy agents from biologicals.

    PubMed

    Farshid, Mahmood; Taffs, Rolf E; Scott, Dorothy; Asher, David M; Brorson, Kurt

    2005-10-01

    The viral and transmissible spongiform encephalopathy (TSE) safety of therapeutics of biological origin (biologicals) is greatly influenced by the nature and degree of variability of the source material and by the mode of purification. Plasma-derived and recombinant DNA products currently have good viral safety records, but challenges remain. In general, large enveloped viruses are easier to remove from biologicals than small 'naked' viruses. Monoclonal antibodies and recombinant DNA biopharmaceuticals are derived from relatively homogeneous source materials and purified by multistep schemes that are robust and amenable to scientific analysis and engineering improvement. Viral clearance is more challenging for blood and cell products, as they are complex and labile. Source selection (e.g. country of origin, deferral for CJD risk factors) currently occupies the front line for ensuring that biologicals are free of TSE agents, but robust methods for their clearance from products are under development.

  12. Transmissible encephalopathies in animals.

    PubMed Central

    Kimberlin, R H

    1990-01-01

    Scrapie in sheep and goats is the best known of the transmissible encephalopathies of animals. The combination of maternal transmission of infection and long incubation periods effectively maintains the infection in flocks. A single sheep gene (Sip) controls both experimental and natural scrapie and the discovery of allelic markers could enable the use of sire selection in the control of the natural disease. Studies of experimental rodent scrapie show that neuroinvasion occurs by spread of infection from visceral lymphoreticular tissues along nerve fibers to mid-thoracic cord. The slowness of scrapie is due to restrictions on replication and cell-to-cell spread of infection affecting neuroinvasion and subsequent neuropathogenesis. Probably both stages in mice are controlled by Sinc gene, the murine equivalent of Sip. The glycoprotein PrP may be the normal product of Sinc gene. Posttranslationally modified PrP forms the disease specific "scrapie associated fibrils" and may also be a constituent of the infectious agent. Scrapie-like diseases have been reported in mink and several species of ruminants including cattle. All of them may be caused by the recycling of scrapie infected sheep material in animal feed. The human health implications are discussed. PMID:2407328

  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). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  16. SCRG1, a potential marker of autophagy in transmissible spongiform encephalopathies.

    PubMed

    Dron, Michel; Bailly, Yannick; Beringue, Vincent; Haeberlé, Anne-Marie; Griffond, Bernadette; Risold, Pierre-Yves; Tovey, Michael G; Laude, Hubert; Dandoy-Dron, Françoise

    2006-01-01

    The Scrg1 gene was initially discovered as one of the genes upregulated in transmissible spongiform encephalopathies (TSE). Scrg1 encodes a highly conserved, cysteine-rich protein expressed principally in the central nervous system. The protein is targeted to the Golgi apparatus and large dense-core vesicles/secretory granules in neurons. We have recently shown that the Scrg1 protein is widely induced in neurons of scrapie-infected mice, suggesting that Scrg1 is involved in the host response to stress and/or the death of neurons. At the ultrastructural level, Scrg1 is associated with dictyosomes of the Golgi apparatus and autophagic vacuoles of degenerative neurons. It is well known that apoptosis plays a major role in the events leading to neuronal cell death in TSE. However, autophagy was identified in experimentally induced scrapie a long time ago and was recently reevaluated as a possible cell death program in prion diseases. The consistent association of Scrg1 with autophagic structures typical of scrapie is in agreement with the recruitment of Golgi-specific proteins in this degradation process and we suggest that Scrg1 might be used as a specific probe to identify neuronal autophagy in TSE.

  17. 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.

  18. [Prion diseases. Subacute spongiform encephalopathies in humans and animals (neural "anthropo- and zooprionoses")].

    PubMed

    Kod'ousek, R

    1999-01-01

    General review concerning current problems of subacute spongiform encephalopathies (Prion-diseases) in humans and in animals. The work is based on the aetiological conception of "Prion" as an allosteric conformational variant of the Prion-protein with autocatalytic "infectious" properties. The therm "Anthropoprionosis" and "Zooprionosis" are recommended by the author for human and animal Prion-diseases. Actual medical problems of various Prion-diseases are discussed in more detail, particularly those of aetiopathogenesis, genetics and molecular-biological principles in Prion-replication as well as the consensual neuropathological and clinical diagnostical criteria. Neuropathological findings are evaluated based on personal experience of diagnosed and/or consulted CJD-cases. On the ultrastructural level the morphological proof of abnormal secondary phagosomes in neurons of the CNS with accumulation of protein material ("prionosomes") is documented. Finally, the risks of CJD and the infectious potential of various organs and contaminated materials are also mentioned. In the methodical part, safety precautions in handling histological material from stereotactic biopsies and necropsies of brain are described, including safety techniques of autopsy in cases of CJD.

  19. Bovine PrP expression levels in transgenic mice influence transmission characteristics of atypical bovine spongiform encephalopathy.

    PubMed

    Wilson, Rona; Hart, Patricia; Piccardo, Pedro; Hunter, Nora; Casalone, Cristina; Baron, Thierry; Barron, Rona M

    2012-05-01

    Until recently, transmissible spongiform encephalopathy (TSE) disease in cattle was thought to be caused by a single agent strain, bovine spongiform encephalopathy (BSE) (classical BSE or BSE-C). However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. These atypical BSE isolates have been previously transmitted to a range of transgenic mouse models overexpressing PrP from different species at different levels, on a variety of genetic backgrounds. To control for genetic background and expression level in the analysis of these isolates, we performed here a comprehensive comparison of the neuropathological and molecular properties of all three BSE agents (BASE, BSE-C and BSE-H) upon transmission into the same gene-targeted transgenic mouse line expressing the bovine prion protein (Bov6) and a wild-type control of the same genetic background. Significantly, upon challenge with these BSE agents, we found that BASE did not produce shorter survival times in these mice compared with BSE-C, contrary to previous studies using overexpressing bovine transgenic mice. Amyloid plaques were only present in mice challenged with atypical BSE and neuropathological features, including intensity of PrP deposition in the brain and severity of vacuolar degeneration were less pronounced in BASE compared with BSE-C-challenged mice.

  20. Bovine PrP expression levels in transgenic mice influence transmission characteristics of atypical bovine spongiform encephalopathy

    PubMed Central

    Wilson, Rona; Hart, Patricia; Piccardo, Pedro; Hunter, Nora; Casalone, Cristina; Baron, Thierry

    2012-01-01

    Until recently, transmissible spongiform encephalopathy (TSE) disease in cattle was thought to be caused by a single agent strain, bovine spongiform encephalopathy (BSE) (classical BSE or BSE-C). However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. These atypical BSE isolates have been previously transmitted to a range of transgenic mouse models overexpressing PrP from different species at different levels, on a variety of genetic backgrounds. To control for genetic background and expression level in the analysis of these isolates, we performed here a comprehensive comparison of the neuropathological and molecular properties of all three BSE agents (BASE, BSE-C and BSE-H) upon transmission into the same gene-targeted transgenic mouse line expressing the bovine prion protein (Bov6) and a wild-type control of the same genetic background. Significantly, upon challenge with these BSE agents, we found that BASE did not produce shorter survival times in these mice compared with BSE-C, contrary to previous studies using overexpressing bovine transgenic mice. Amyloid plaques were only present in mice challenged with atypical BSE and neuropathological features, including intensity of PrP deposition in the brain and severity of vacuolar degeneration were less pronounced in BASE compared with BSE-C-challenged mice. PMID:22302882

  1. 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

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

    PubMed

    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.

  3. Unique properties of the classical bovine spongiform encephalopathy strain and its emergence from H-type bovine spongiform encephalopathy substantiated by VM transmission studies.

    PubMed

    Bencsik, Anna; Leboidre, Mikael; Debeer, Sabine; Aufauvre, Claire; Baron, Thierry

    2013-03-01

    In addition to classical bovine spongiform encephalopathy (C-BSE), which is recognized as being at the origin of the human variant form of Creutzfeldt-Jakob disease, 2 rare phenotypes of BSE (H-type BSE [H-BSE] and L-type BSE [L-BSE]) were identified in 2004. H-type BSE and L-BSE are considered to be sporadic forms of prion disease in cattle because they differ from C-BSE with respect to incubation period, vacuolar pathology in the brain, and biochemical properties of the protease-resistant prion protein (PrP) in natural hosts and in some mouse models that have been tested. Recently, we showed that H-BSE transmitted to C57Bl/6 mice resulted in a dissociation of the phenotypic features, that is, some mice showed an H-BSE phenotype, whereas others had a C-BSE phenotype. Here, these 2 phenotypes were further studied in VM mice and compared with cattle C-BSE, H-BSE, and L-BSE. Serial passages from the C-BSE-like phenotype on VM mice retained similarities with C-BSE. Moreover, our results indicate that strains 301V and 301C derived from C-BSE transmitted to VM and C57Bl/6 mice, respectively, are fundamentally the same strain. These VM transmission studies confirm the unique properties of the C-BSE strain and support the emergence of a strain that resembles C-BSE from H-BSE.

  4. Pyroglutamyl-N-terminal prion protein fragments in sheep brain following the development of transmissible spongiform encephalopathies

    PubMed Central

    Gielbert, Adriana; Thorne, Jemma K.; Hope, James

    2015-01-01

    Protein misfolding, protein aggregation and disruption to cellular proteostasis are key processes in the propagation of disease and, in some progressive neurodegenerative diseases of the central nervous system, the misfolded protein can act as a self-replicating template or prion converting its normal isoform into a misfolded copy of itself. We have investigated the sheep transmissible spongiform encephalopathy, scrapie, and developed a multiple selected reaction monitoring (mSRM) mass spectrometry assay to quantify brain peptides representing the “ragged” N-terminus and the core of ovine prion protein (PrPSc) by using Q-Tof mass spectrometry. This allowed us to identify pyroglutamylated N-terminal fragments of PrPSc at residues 86, 95 and 101, and establish that these fragments were likely to be the result of in vivo processes. We found that the ratios of pyroglutamylated PrPSc fragments were different in sheep of different breeds and geographical origin, and our expanded ovine PrPSc assay was able to determine the ratio and allotypes of PrP accumulating in diseased brain of PrP heterozygous sheep; it also revealed significant differences between N-terminal amino acid profiles (N-TAAPs) in other types of ovine prion disease, CH1641 scrapie and ovine BSE. Variable rates of PrP misfolding, aggregation and degradation are the likely basis for phenotypic (or strain) differences in prion-affected animals and our mass spectrometry-based approach allows the simultaneous investigation of factors such as post-translational modification (pyroglutamyl formation), conformation (by N-TAAP analysis) and amino-acid polymorphisms (allotype ratio) which affect the kinetics of these proteostatic processes. PMID:25988175

  5. Characterization of an unusual transmissible spongiform encephalopathy in goat by transmission in knock-in transgenic mice.

    PubMed

    Wilson, Rona; King, Declan; Hunter, Nora; Goldmann, Wilfred; Barron, Rona M

    2013-08-01

    Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disorder of cattle, and its transmission to humans through contaminated food is thought to be the cause of the variant form of Creutzfeldt-Jakob disease. BSE is believed to have spread from the recycling in cattle of ruminant tissue in meat and bone meal (MBM). However, during this time, sheep and goats were also exposed to BSE-contaminated MBM. Both sheep and goats are experimentally susceptible to BSE, and while there have been no reported natural BSE cases in sheep, two goat BSE field cases have been documented. While cases of BSE are rare in small ruminants, the existence of scrapie in both sheep and goats is well established. In the UK, during 2006-2007, a serious outbreak of clinical scrapie was detected in a large dairy goat herd. Subsequently, 200 goats were selected for post-mortem examination, one of which showed biochemical and immunohistochemical features of the disease-associated prion protein (PrP(TSE)) which differed from all other infected goats. In the present study, we investigated this unusual case by performing transmission bioassays into a panel of mouse lines. Following characterization, we found that strain properties such as the ability to transmit to different mouse lines, lesion profile pattern, degree of PrP deposition in the brain and biochemical features of this unusual goat case were neither consistent with goat BSE nor with a goat scrapie herdmate control. However, our results suggest that this unusual case has BSE-like properties and highlights the need for continued surveillance.

  6. Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model

    PubMed Central

    Bencsik, Anna; Biacabe, Anne-Gaëlle; Morignat, Eric; Bessen, Richard A.

    2007-01-01

    Transmissible mink encepholapathy (TME) is a foodborne transmissible spongiform encephalopathy (TSE) of ranch-raised mink; infection with a ruminant TSE has been proposed as the cause, but the precise origin of TME is unknown. To compare the phenotypes of each TSE, bovine-passaged TME isolate and 3 distinct natural bovine spongiform encephalopathy (BSE) agents (typical BSE, H-type BSE, and L-type BSE) were inoculated into an ovine transgenic mouse line (TgOvPrP4). Transgenic mice were susceptible to infection with bovine-passaged TME, typical BSE, and L-type BSE but not to H-type BSE. Based on survival periods, brain lesions profiles, disease-associated prion protein brain distribution, and biochemical properties of protease-resistant prion protein, typical BSE had a distint phenotype in ovine transgenic mice compared to L-type BSE and bovine TME. The similar phenotypic properties of L-type BSE and bovine TME in TgOvPrP4 mice suggest that L-type BSE is a much more likely candidate for the origin of TME than is typical BSE. PMID:18258040

  7. Phenotypic similarity of transmissible mink encephalopathy in cattle and L-type bovine spongiform encephalopathy in a mouse model.

    PubMed

    Baron, Thierry; Bencsik, Anna; Biacabe, Anne-Gaëlle; Morignat, Eric; Bessen, Richard A

    2007-12-01

    Transmissible mink encepholapathy (TME) is a foodborne transmissible spongiform encephalopathy (TSE) of ranch-raised mink; infection with a ruminant TSE has been proposed as the cause, but the precise origin of TME is unknown. To compare the phenotypes of each TSE, bovine-passaged TME isolate and 3 distinct natural bovine spongiform encephalopathy (BSE) agents (typical BSE, H-type BSE, and L-type BSE) were inoculated into an ovine transgenic mouse line (TgOvPrP4). Transgenic mice were susceptible to infection with bovine-passaged TME, typical BSE, and L-type BSE but not to H-type BSE. Based on survival periods, brain lesions profiles, disease-associated prion protein brain distribution, and biochemical properties of protease-resistant prion protein, typical BSE had a distint phenotype in ovine transgenic mice compared to L-type BSE and bovine TME. The similar phenotypic properties of L-type BSE and bovine TME in TgOvPrP4 mice suggest that L-type BSE is a much more likely candidate for the origin of TME than is typical BSE.

  8. [Maternal transmission or bovine spongiform encephalopathy in the case of "Cindy" disproved].

    PubMed

    Baumgartner, B G; Margan, U; Olek, K; Wagner, V; Brenig, B

    1997-09-01

    On December 27th, 1996 a Galloway cattle named "Cindy" died of bovine spongiform encephalopathy (BSE) in Höxter. So far all cases of BSE reported in Germany have been imported from the UK. However, the identity and origin of "Cindy" was not clear. DNA sequence analysis of the mitochondrial D-loop region and DNA typing of micro-satellite sites finally revealed that "Cindy" was imported from the UK as well.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  10. Bad news and good news: what the dentist needs to know about transmissible spongiform encephalopathies.

    PubMed

    Gonzales, T S; Rushing, E J

    1998-05-01

    Since reports of the "mad cow disease" epidemic in Great Britain erupted in the international press, sensational and intimidating articles about the risk that bovine spongiform encephalopathy and related diseases may pose to humans have appeared. The bad news is that compelling scientific evidence suggests so-called prion disease can and has infected humans, although the overall risk appears to be low. Furthermore, at present, there is no reliable antemortem diagnosis, specific treatment, or vaccine to prevent the disease. The agent thought to be responsible for this unusual class of disease is a rogue protein (called a prion) that, unlike all other agents known to cause infectious disease, contains neither DNA nor RNA. According to a popular hypothesis, normal membrane-associated prion proteins undergo conformational changes that can cause disease. The "bad" prion forms cause holes or a spongy appearance in the brain in all disease variants, hence the generic designation of spongiform encephalopathy. The good news is that risk for exposure to prion disease is exceedingly remote in the dental practice and that current universal infection control procedures are probably sufficient.

  11. 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

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

    PubMed

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

    2015-07-13

    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.

  13. 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.

  14. Use of bovine recombinant prion protein and real-time quaking-induced conversion to detect transmissible mink encephalopathy prions and discriminate classical and atypical L- and H-type bovine spongiform encephalopathy

    USDA-ARS?s Scientific Manuscript database

    Prions are amyloid-forming proteins that cause transmissible spongiform encephalopathies through a process involving conversion from normal cellular prion protein to pathogenic misfolded conformation. This conversion has been used for in vitro assays including serial protein misfolding amplification...

  15. Gerstmann-Sträussler-Scheinker syndrome,fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies.

    PubMed

    Collins, S; McLean, C A; Masters, C L

    2001-09-01

    Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), fatal familial insomnia (FFI) and kuru constitute major human prion disease phenotypes. Each has been successfully transmitted in animal models and all are invariably fatal neurodegenerative disorders, with the brains of affected individuals harbouring variable amounts of an abnormal, protease-resistant form of the prion protein (PrPres), which is inextricably linked to pathogenesis and transmissibility. Classical sporadic CJD is the most common human transmissible spongiform encephalopathy (TSE), but recently the variant form (vCJD), first described in the UK in 1996, has drawn considerable attention. In contrast to sporadic CJD, FFI and GSS are almost invariably genetically determined TSEs, caused by a range of mutations within the open reading frame of the prion protein gene (PRNP) on chromosome 20. By definition, the nosologic term FFI is reserved for patients manifesting prominent insomnia, generally in combination with dysautonomia, myoclonus, and eventual dementia, with the predominant pathologic changes lying within the thalami and a specific underlying mutation in PRNP. GSS, however, encompasses a more diverse clinical spectrum ranging from progressive cerebellar ataxia or spastic paraparesis (both usually in combination with dementia), to isolated cognitive impairment resembling Alzheimer's disease. Additional extra-pyramidal features, which may respond to dopaminergic therapy can also be seen. Neuropathological findings are also relatively diverse, partly overlapping with those found in Alzheimer's disease, especially the presence of neurofibrillary tangles (NFTs). Although GSS and FFI in their classical forms are differentiable clinical profiles, such divisions may have no intrinsic biological validity given the considerable intra-familial clinico-pathological diversity so commonly seen. Kuru constitutes a horizontally transmitted prion disease, which after a lengthy

  16. A direct relationship between the partitioning of the pathogenic prion protein and transmissible spongiform encephalopathy infectivity during the purification of plasma proteins.

    PubMed

    Lee, D C; Stenland, C J; Miller, J L; Cai, K; Ford, E K; Gilligan, K J; Hartwell, R C; Terry, J C; Rubenstein, R; Fournel, M; Petteway, S R

    2001-04-01

    Experimental evidence from rodent models indicates that blood can contain transmissible spongiform encephalopathy (TSE) infectivity, which suggests a potential risk for TSE transmission via proteins isolated from human plasma. Because methods that can reduce TSE infectivity typically are detrimental to protein function, infectivity must be removed to ensure the safety of these therapeutic proteins. Animal bioassays are conventionally used to detect infectivity, but the pathogenic form of the prion protein (PrP(Sc)) can serve as a marker for TSE infectivity. Seven plasma protein-purification steps were performed after the plasma intermediates were spiked with TSE-infected material. Resulting fractions were analyzed for PrP(Sc) by using a Western blot assay and for TSE infectivity by using an animal bioassay. Western blots were quantitated by an endpoint dilution analysis, and infectivity titers were calculated by the Spearman-Kärber method. PrP(Sc) partitioning paralleled TSE infectivity partitioning, regardless of the nature of the protein-purification step. The detection ranges for PrP(Sc) and infectivity were 0 to 5.3 log and 1.1 to 8.9 log median infectious dose per unit, respectively. Clearance of PrP(Sc) and infectivity ranged from 1.0 to 6.0 log. Purification steps for isolating therapeutic proteins from human plasma showed the removal of both PrP(Sc) and TSE infectivity. PrP(Sc) partitioning coincided with infectivity partitioning, which showed a close relationship between PrP(Sc) and TSE infectivity. By exploiting this association, the in vitro Western blot assay for PrP(Sc) was valuable for estimating the partitioning of TSE infectivity during plasma protein purification.

  17. 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

  18. 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.

  19. Animal health and price transmission along livestock supply chains.

    PubMed

    Aragrande, M; Canali, M

    2017-04-01

    Animal health diseases can severely affect the food supply chain by causing variations in prices and market demand. Price transmission analysis reveals in what ways price variations are transmitted along the supply chain, and how supply chains of substitute products and different regional markets are also affected. In perfect markets, a price variation would be completely and instantaneously transmitted across the different levels of the supply chain: producers, the processing industry, retailers and consumers. However, empirical studies show that food markets are often imperfect, with anomalies or asymmetries in price transmission and distortions in the distribution of market benefits. This means, for instance, that a price increase at the consumer level may not be transmitted from retailers to processors and producers; yet, on the other hand, price falls may rapidly affect the upstream supply chain. Market concentration and the consequent exertion of market power in key segments of the supply chain can explain price transmission asymmetries and their distributional effects, but other factors may also be involved, such as transaction costs, scale economies, and imperfect information. During the bovine spongiform encephalopathy (BSE) crisis, asymmetric price transmission in the beef supply chain and related meat markets determined distributional effects among sectors. After the spread of the BSE food scare, the fall in demand marginally affected the price paid to retailers, but producers and wholesalers suffered much more, in both price reductions and the time needed to recover to precrisis demand. Price transmission analysis investigates how animal health crises create different economic burdens for various types of stakeholder, and provides useful socioeconomic insights when used with other tools.

  20. 75 FR 55803 - Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... the variant Creutzfeldt-Jakob disease (vCJD) agent in U.S.-licensed plasma-derived Factor VIII and (2) labeling of blood and blood components and plasma-derived products, including plasma-derived albumin and products containing plasma-derived albumin, to address the possible risk of transmission of vCJD. On...

  1. PrP-C1 fragment in cattle brains reveals features of the transmissible spongiform encephalopathy associated PrP(sc).

    PubMed

    Serra, Fabienne; Müller, Joachim; Gray, John; Lüthi, Ramona; Dudas, Sandor; Czub, Stefanie; Seuberlich, Torsten

    2017-03-15

    Three different types of bovine spongiform encephalopathy (BSE) are known and supposedly caused by distinct prion strains: the classical (C-) BSE type that was typically found during the BSE epidemic, and two relatively rare atypical BSE types, termed H-BSE and L-BSE. The three BSE types differ in the molecular phenotype of the disease associated prion protein, namely the N-terminally truncated proteinase K (PK) resistant prion protein fragment (PrP(res)). In this study, we report and analyze yet another PrP(res) type (PrP(res-2011)), which was found in severely autolytic brain samples of two cows in the framework of disease surveillance in Switzerland in 2011. Analysis of brain tissues from these animals by PK titration and PK inhibitor assays ruled out the process of autolysis as the cause for the aberrant PrP(res) profile. Immunochemical characterization of the PrP fragments present in the 2011 cases by epitope mapping indicated that PrP(res-2011) corresponds in its primary sequence to the physiologically occurring PrP-C1 fragment. However, high speed centrifugation, sucrose gradient assay and NaPTA precipitation revealed biochemical similarities between PrP(res-2011) and the disease-associated prion protein found in BSE affected cattle in terms of detergent insolubility, PK resistance and PrP aggregation. Although it remains to be established whether PrP(res-2011) is associated with a transmissible disease, our results point out the need of further research on the role the PrP-C1 aggregation and misfolding in health and disease.

  2. Use of bovine recombinant prion protein and real-time quaking-induced conversion to detect cattle transmissible mink encephalopathy prions and discriminate classical and atypical L- and H-Type bovine spongiform encephalopathy

    PubMed Central

    Hwang, Soyoun; Greenlee, Justin J.

    2017-01-01

    Prions are amyloid-forming proteins that cause transmissible spongiform encephalopathies through a process involving conversion from the normal cellular prion protein to the pathogenic misfolded conformation (PrPSc). This conversion has been used for in vitro assays including serial protein misfolding amplification and real-time quaking induced conversion (RT-QuIC). RT-QuIC can be used for the detection of prions in a variety of biological tissues from humans and animals. Extensive work has been done to demonstrate that RT-QuIC is a rapid, specific, and highly sensitive prion detection assay. RT-QuIC uses recombinant prion protein to detect minute amounts of PrPSc. RT-QuIC has been successfully used to detect PrPSc from different prion diseases with a variety of substrates including hamster, human, sheep, bank vole, bovine and chimeric forms of prion protein. However, recombinant bovine prion protein has not been used to detect transmissible mink encephalopathy (TME) or to differentiate types of bovine spongiform encephalopathy (BSE) in samples from cattle. We evaluated whether PrPSc from TME and BSE infected cattle can be detected with RT-QuIC using recombinant bovine prion proteins, and optimized the reaction conditions to specifically detect cattle TME and to discriminate between classical and atypical BSE by conversion efficiency. We also found that substrate composed of the disease associated E211K mutant protein can be effective for the detection of TME in cattle and that wild type prion protein appears to be a practical substrate to discriminate between the different types of BSEs. PMID:28225797

  3. Use of bovine recombinant prion protein and real-time quaking-induced conversion to detect cattle transmissible mink encephalopathy prions and discriminate classical and atypical L- and H-Type bovine spongiform encephalopathy.

    PubMed

    Hwang, Soyoun; Greenlee, Justin J; Nicholson, Eric M

    2017-01-01

    Prions are amyloid-forming proteins that cause transmissible spongiform encephalopathies through a process involving conversion from the normal cellular prion protein to the pathogenic misfolded conformation (PrPSc). This conversion has been used for in vitro assays including serial protein misfolding amplification and real-time quaking induced conversion (RT-QuIC). RT-QuIC can be used for the detection of prions in a variety of biological tissues from humans and animals. Extensive work has been done to demonstrate that RT-QuIC is a rapid, specific, and highly sensitive prion detection assay. RT-QuIC uses recombinant prion protein to detect minute amounts of PrPSc. RT-QuIC has been successfully used to detect PrPSc from different prion diseases with a variety of substrates including hamster, human, sheep, bank vole, bovine and chimeric forms of prion protein. However, recombinant bovine prion protein has not been used to detect transmissible mink encephalopathy (TME) or to differentiate types of bovine spongiform encephalopathy (BSE) in samples from cattle. We evaluated whether PrPSc from TME and BSE infected cattle can be detected with RT-QuIC using recombinant bovine prion proteins, and optimized the reaction conditions to specifically detect cattle TME and to discriminate between classical and atypical BSE by conversion efficiency. We also found that substrate composed of the disease associated E211K mutant protein can be effective for the detection of TME in cattle and that wild type prion protein appears to be a practical substrate to discriminate between the different types of BSEs.

  4. Kangaroo rats exhibit spongiform degeneration of the central auditory system similar to that found in gerbils.

    PubMed

    McGinn, M D; Faddis, B T

    1997-02-01

    Kangaroo rats develop spongiform degeneration of the central auditory system similar to that seen in the gerbil. Light microscopic and transmission electron microscopic study of the cochlear nucleus and auditory nerve root (ANR) of Dipodomys deserti and D. merriami show that spongiform lesions develop in dendrites and oligodendrocytes of the cochlear nucleus and in oligodendrocytes of the ANR that are morphologically indistinguishable from those extensively described in the Mongolian gerbil, Meriones unguiculatus. As in Mongolian gerbils, the spongiform degeneration in Dipodomys were much more numerous in animals continually exposed to modest levels of low-frequency noise (< 75 dB SPL). The kangaroo rats with extensive spongiform degeneration also show slightly, but significantly, elevated auditory brainstem evoked response (ABR) thresholds to low-frequency stimuli, a result also found in Mongolian gerbils. These results suggest that the elevated ABR thresholds may be the result of spongiform degeneration. Because low-frequency noise-induced spongiform degeneration has now been shown in the cochlear nucleus of animals from separate families of Rodentia (Heteromyidae and Muridae), the possibility should be investigated that similar noise-induced degenerative changes occur in the central auditory system of other mammals with good low-frequency hearing.

  5. 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

  6. Susceptibility of European Red Deer (Cervus elaphus elaphus) to Alimentary Challenge with Bovine Spongiform Encephalopathy

    PubMed Central

    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

  7. 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

  8. Further characterisation of transmissible spongiform encephalopathy phenotypes after inoculation of cattle with two temporally separated sources of sheep scrapie from Great Britain.

    PubMed

    Konold, Timm; Nonno, Romolo; Spiropoulos, John; Chaplin, Melanie J; Stack, Michael J; Hawkins, Steve A C; Cawthraw, Saira; Wilesmith, John W; Wells, Gerald A H; Agrimi, Umberto; Di Bari, Michele A; Andréoletti, Olivier; Espinosa, Juan C; Aguilar-Calvo, Patricia; Torres, Juan M

    2015-07-24

    The infectious agent responsible for the bovine spongiform encephalopathy (BSE) epidemic in Great Britain is a transmissible spongiform encephalopathy (TSE) strain with uniform properties but the origin of this strain remains unknown. Based on the hypothesis that classical BSE may have been caused by a TSE strain present in sheep, cattle were inoculated intracerebrally with two different pools of brains from scrapie-affected sheep sourced prior to and during the BSE epidemic to investigate resulting disease phenotypes and characterise their causal agents by transmission to rodents. As reported in 2006, intracerebral inoculation of cattle with pre-1975 and post-1990 scrapie brain pools produced two distinct disease phenotypes, which were unlike classical BSE. Subsequent to that report none of the remaining cattle, culled at 10 years post inoculation, developed a TSE. Retrospective Western immunoblot examination of the brains from TSE cases inoculated with the pre-1975 scrapie pool revealed a molecular profile similar to L-type BSE. The inoculation of transgenic mice expressing the bovine, ovine, porcine, murine or human prion protein gene and bank voles with brains from scrapie-affected cattle did not detect classical or atypical BSE strains but identified two previously characterised scrapie strains of sheep. Characterisation of the causal agents of disease resulting from exposure of cattle to naturally occurring scrapie agents sourced in Great Britain did not reveal evidence of classical or atypical BSE, but did identify two distinct previously recognised strains of scrapie. Although scrapie was still recognizable upon cattle passage there were irreconcilable discrepancies between the results of biological strain typing approaches and molecular profiling methods, suggesting that the latter may not be appropriate for the identification and differentiation of atypical, particularly L-type, BSE agents from cattle experimentally infected with a potential mixture of

  9. 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.

  10. Profiling the culprit in Alzheimer's disease (AD): bacterial toxic proteins - Will they be significant for the aetio-pathogenesis of AD and the transmissible spongiform encephalopathies?

    PubMed

    Schmitt, H Peter

    2007-01-01

    The aetiology of Alzheimer's disease (AD) and the transmissible spongiform encephalopathies (tSEs) is still elusive. The concept that prion protein (PrP(Sc)) is the aetiological agent (infectious protein) in the tSEs has recently been questioned. In AD, the cause of the aberrant cleavage of the beta-amyloid precursor protein (APP), resulting in the production of amyloidogenic Abeta fragments, has yet remained obscure. Moreover, the amyloid hypothesis of AD has been seriously challenged. In both AD and the tSEs, pathogens of various nature, including bacteria, have been discussed as possible causal factors. However, aetiological considerations have completely neglected microbial products such as the bacterial toxic proteins (BTPs). The present paper is aimed at drawing a "culprit profile" of these toxic molecules that can exert, at low-dosage, neuro-degeneration through various effects. Clearly, BTPs may affect cell-surface receptors including modulatory amine transmitter receptor expression, block neuro-transmitter release, increase intra-cellular Ca(2+) levels, affect intra-cellular signal transduction, change cyto-skeletal processing, alter synaptic transmission, influence APP proteolysis, interact with cell surface proteins like PrP(C) or their GPI anchors, act as chaperones inducing conformational change in proteins (e.g., PrP(C) to PrP(Sc)), alter lipid membrane integrity by affecting phospholipases or forming pores and channels, induce vacuolar (spongiform) change and elicit inflammatory reactions with cytokine production including cytokines that were demonstrated in the AD brain. Like PrP(Sc), BTPs can be heat-stable and acid-resistant. BTPs can meet the key-proteins of AD and tSEs in the lipid-rich domains of the plasma membrane called rafts. Basically, this might enable them to initiate a large variety of unfavourable molecular events, eventually resulting in pathogenetic cascades as in AD and the tSEs. All in all, their profile lends support to the

  11. Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies: use of a rapid whole homogenate, protease-free assay

    PubMed Central

    2013-01-01

    Background Transmissible Spongiform Encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in cervids, transmissible mink encephalopathy (TME), and bovine spongiform encephalopathy (BSE), are fatal diseases of the nervous system associated with accumulation of misfolded prion protein (PrPSc). Different strains of TSEs exist, associated with different PrPSc conformations that can be probed by the stability assay, in which PrPSc is treated with increasing concentrations of the denaturant guanidine hydrochloride (GdnHCl). Results Here, we provide the first comprehensive application of a rapid, protease-free version of the GdnHCl stability assay to brain tissue from cattle experimentally infected with various TSE isolates. Consistent with previous findings from a single Japanese isolate, the L-type isolates of BSE are not distinguishable from classical BSE in this assay. In contrast, H-type isolates of BSE, including our unique isolate of E211K BSE, exhibit higher stability than classical BSE, suggesting that its increased protection against protease digestion at the BSE N-terminus is associated with a higher stability in GdnHCl. While the difference in stability in our version of the assay is likely not large enough for effective use in a diagnostic laboratory setting, the use of alternative experimental conditions may enhance this effect. TSEs from other natural host species that have been passaged in cattle, including CWD and TME, were not distinguishable from classical BSE, while isolates of cattle passaged scrapie exhibited a slight increase in stability as compared to classical BSE. Conclusions These results suggest that the core of PrPSc, as probed in this assay, has similar stability properties among cattle-passaged TSE isolates and that the conformational differences that lead to changes in the proteinase K cleavage site do not cause large changes in the stability of PrPSc from TSE-affected cattle. However, the stability differences

  12. Transcript level of erythroid differentiation-related factor, a candidate surrogate marker for transmissible spongiform encephalopathy diseases in blood, shows a broad range of variation in healthy individuals.

    PubMed

    Glock, Barbara; Winter, Maya; Rennhofer, Simone O; Brunhölzl, Elisabeth; Tröscher, Doris; Reisacher, Rosemarie B K; Mayr, Wolfgang R

    2003-12-01

    In 2001, it was demonstrated that the expression of the erythroid differentiation-related factor (EDRF) is reduced in lymphatic tissues of rodents and cattle as well as in whole blood of sheep that suffer from transmissible spongiform encephalopathy. To determine whether the normal range of EDRF expression varies in healthy individuals, mRNA levels were measured in whole blood samples from 106 healthy blood donors by quantitative real-time RT-PCR. Furthermore, the correlations of transcript levels with individual physical characteristics were analyzed. In addition, EDRF expression was examined in total RNA samples from a lymph node and the intestine. The data show that EDRF mRNA levels in healthy persons vary within a total range of 2 log units as well as they display a weak correlation with body height. Furthermore, it was found that EDRF is also expressed in lymph nodes and the intestine. Owing to its broad range of variation, measuring the EDRF expression does not seem to be a good surrogate marker, unless an altered expression is distinctively different from the varying level in healthy humans.

  13. 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.

  14. Disease transmission in animal transfer networks.

    PubMed

    Sintayehu, Dejene W; Prins, H H T; Heitkönig, I M A; de Boer, W F

    2017-02-01

    Infectious diseases transmission is strongly determined by who contacts whom. Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a worldwide burden for animal populations. One of the major transmission mechanism between herd is the transfer of infectious animal. In East Africa, pastoralists may receive or bestow livestock to create and strengthen social relationships. Here, we used a network approach to examine the relative importance of such cattle transfer in the transmission of bTB. First, a total of 2550 cattle from 102 herds were tested using the comparative intradermal tuberculin test to assess the presence of bTB infected cattle in the herd. A herd was considered bTB positive if it had at least one tuberculin reactor animal. Next, we calculated the centrality of each herd in the cattle transfer network using four established measures of social network centralization: degree, betweenness, closeness and fragmentation. The relationships between the network centrality measures and bTB infection were examined using generalized linear mixed models (GLMM). We found that a herd's in-degree in the social network was positively correlated with the risk of being infected with bTB (b=4.2, 95%CI=2.1-5.7; p<0.001). A herd that was close to many others (i.e., had a higher closeness index) had a larger chance of acquiring bTB infection (b=2.1, 95%CI=1.4-2.8; p<0.001). Betweenness centrality was also positively associated with the presence of bTB infection. There was a negative relationship between the fragmentation index and bTB infection (b=-2.7, 95%CI=-4.9-1.3; p<0.001). The study clearly demonstrated that the extent to which a herd is connected within a network has significant implications for its probability of being infected. Further, the results are in accordance with our expectation that connectivity and the probability that a herd will transmit the disease to other herds in the network are related. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Typical and atypical cases of bovine spongiform encephalopathy

    USDA-ARS?s Scientific Manuscript database

    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...

  16. A quantitative assessment of the risk of transmission of bovine spongiform encephalopathy by tallow-based calf milk-replacer.

    PubMed

    Paisley, Larry G; Hostrup-Pedersen, Julie

    2004-04-30

    A Monte Carlo simulation model was constructed to assess the risk of BSE transmission to calves by calf milk-replacer (CMR). We assumed that any BSE infectivity in the CMR would be associated with the allowable levels of impurities in tallow used to manufacture the milk-replacer. Simulations used three different levels of impurities, six different distributions of the BSE infectivity titers of CNS tissues and with and without inclusion of specified risk material (SRM). Our results suggest that tallow-based CMR could have been responsible for some BSE infections in nearly all simulations. The reduction in the allowable impurities in tallow and the exclusion of SRM have greatly reduced--but have not eliminated--the risk of BSE transmission by CMR The results of the simulations are associated with much uncertainty.

  17. Fukuoka-1 strain of transmissible spongiform encephalopathy agent infects murine bone marrow-derived cells with features of mesenchymal stem cells

    PubMed Central

    Cervenakova, Larisa; Akimov, Sergey; Vasilyeva, Irina; Yakovleva, Oksana; McKenzie, Carroll; Cervenak, Juraj; Piccardo, Pedro; Asher, David M.

    2011-01-01

    BACKGROUND The possible risk of iatrogenic transmissible spongiform encephalopathies (TSEs, prion diseases) from transplantation of bone marrow-derived mesenchymal stem cells (MSCs) is uncertain. While most cell lines resist infection, a few propagate TSE agents. STUDY DESIGN AND METHODS We generated MSC-like (MSC-L) cell cultures from bone marrow (BM) of mice inoculated with the human-derived Fukuoka-1 (Fu) strain of TSE agent. Cultured cells were characterized for various markers and cellular prion protein (PrPC) by FACS and for PrPC and its pathologic TSE-associated form (PrPTSE) by Western blotting (WB). Cell cultures were tested for their susceptibility to infection with Fu in vitro. Infectivity of one Fu-infected cell culture was assayed in mice. RESULTS BM cells from Fu-infected mice expressed neither PrPC nor PrPTSE after three days in culture as demonstrated by WB. Cells adherent to plastic and maintained under two different culture conditions became spontaneously immortalized and began to express PrPC at about the same time. One culture became transformed shortly after exposure to Fu in vitro and remained persistently infected, continuously generating PrPTSE through multiple passages; infectivity of cultured cells was confirmed by intracerebral inoculation of lysates into mice. Both persistently TSE-infected and uninfected cells expressed a number of typical MSC markers. CONCLUSION BM-derived MSC-L cells of mice became persistently infected with the Fu agent under certain conditions in culture—conditions that differ substantially from those currently used to develop investigational human stem cell therapies. PMID:21303371

  18. 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.

  19. 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

    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 growth

  20. Transmissible Spongiform Encephalopathies (Prion Diseases)

    MedlinePlus

    ... Symptoms of TSEs vary, but they commonly include personality changes, psychiatric problems such as depression, lack of ... Symptoms of TSEs vary, but they commonly include personality changes, psychiatric problems such as depression, lack of ...

  1. 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...

  2. 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...

  3. [Prions: where do we stand 20 years after the appearance of bovine spongiform encephalopathy?].

    PubMed

    Crozet, Carole; Lehmann, Sylvain

    2007-12-01

    Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) identified twenty years ago in the British cattle herds. Creutzfeldt-Jakob disease (CJD) is a TSE that occurs in humans. In 1996, scientists found a possible link between BSE and a new variant of CJD (vCJD). The fact that the non conventional infectious agent of TSE, named prions, could cross the species barrier from cattle to human through meat consumption, raised a tremendous concern for public safety in Europe. This led to the development in the following two decades of substantial and expensive measures to contain BSE and prevent its transmission to humans. In parallel, scientific programs have been funded to progress through the comprehension of the physiopathology of these fatal disorders. In Europe, the BSE epidemics is now ending and the number of cases is decreasing thanks to the strict control of animal foodstuff that was the main source of prion contamination. Only a small number of vCJD have been detected, however, additional concerns have been raised recently for public safety as secondary transmission of CJD through medical procedure and blood transfusion is possible. In addition, the possibility that the BSE was transmitted to other animals including small ruminants is also worrisome. Research efforts are now focussing on decontamination and ante mortem diagnosis of TSE to prevent animal and human transmission. However, needs for fundamental research are still important as many questions remain to be addressed to understand the mechanism of prion transmission, as well as its pathogenesis.

  4. 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.

  5. 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

  6. Bovine Spongiform Encephalopathy

    USDA-ARS?s Scientific Manuscript database

    Bovine spongiform encephalopathy (BSE) is caused by a novel contagion, known to as a prion. Prions are proteins capable of converting a normal cellular protein into a prion, thereby propagating an infection. BSE is the first known prion zoonotic. As such it has attracted broad scientific and, to a r...

  7. 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.

  8. Bovine spongiform encephalopathy: a tipping point in One Health and Food Safety.

    PubMed

    Hope, James

    2013-01-01

    Bovine spongiform encephalopathy (BSE) is a protein misfolding disease of cattle which belongs to the group of transmissible spongiform encephalopathies (TSEs) or prion diseases. This group also includes scrapie in sheep and goats, chronic wasting disease (CWD) of cervids and Creutzfeldt-Jakob disease (CJD) humans. The first case of BSE was recognised in England in 1986 as a progressive, neurological condition where affected animals behaved abnormally, exhibited anxiety, ataxia, hypersensitivity to touch and noise and poor body condition. Spongiform change was observed in the brain stem of cattle at post-mortem and its similarity to scrapie in sheep stimulated biochemical investigation and transmission studies which confirmed it as a novel prion disease of cattle. Epidemiological analysis of the initial cases of disease implicated a common extended source of infection, likely to be related to feed, and stimulated a series of control measures designed to restrict feeding of mammalian-derived protein to ruminants in various parts of the United Kingdom and to prevent the use of various bovine offals in feed or food production. This article outlines the rise and fall of the incidence of BSE in the UK and Europe, its classification as a zoonotic disease with the emergence of variant CJD, the implications of it as a prion disease and challenge its diagnosis and control continues to represent worldwide.

  9. Zoonotic Hepatitis E Virus: Classification, Animal Reservoirs and Transmission Routes

    PubMed Central

    Doceul, Virginie; Bagdassarian, Eugénie; Demange, Antonin; Pavio, Nicole

    2016-01-01

    During the past ten years, several new hepatitis E viruses (HEVs) have been identified in various animal species. In parallel, the number of reports of autochthonous hepatitis E in Western countries has increased as well, raising the question of what role these possible animal reservoirs play in human infections. The aim of this review is to present the recent discoveries of animal HEVs and their classification within the Hepeviridae family, their zoonotic and species barrier crossing potential, and possible use as models to study hepatitis E pathogenesis. Lastly, this review describes the transmission pathways identified from animal sources. PMID:27706110

  10. Transmission of Helicobacter pyori in an animal model.

    PubMed

    Cellini, L; Marzio, L; Ferrero, G; Del Vino, A; Di Campli, E; Grossi, L; Toracchio, S; Artese, L

    2001-01-01

    An experimental murine model was studied to evaluate the orogastrointestinal colonization of Helicobacter pylori and the animal-to-animal transmission. Balb/C mice were infected with H. pylori and housed with uninoculated mice in cages with and without a grate on the floor. Mice were killed after 7, 14, 30, and 45 days, and samples from the esophagus, stomach, small intestine, colon, and rectum were analyzed for H. pylori by PCR and immunohistochemistry and for histological changes. Bacterial colonization was assessed also by culture from stomach samples. H. pylori was cultured by stomach samples of infected mice at 7, 14, and 30 days. Using PCR and immunohistochemistry, H. pylori was detected in inoculated and uninoculated mice in all areas examined, with an high percentage of positive samples in the esophagus and stomach. Moreover transmission was detected, without differences, regardless of whether mice were housed with or without a grate on the floor, supporting an orooral animal transmission.

  11. Evidence of in utero transmission of classical scrapie in sheep.

    PubMed

    Spiropoulos, John; Hawkins, Stephen A C; Simmons, Marion M; Bellworthy, Susan J

    2014-04-01

    Classical scrapie is one of the transmissible spongiform encephalopathies (TSEs), a group of fatal infectious diseases that affect the central nervous system (CNS). Classical scrapie can transmit laterally from ewe to lamb perinatally or between adult animals. Here we report detection of infectivity in tissues of an unborn fetus, providing evidence that in utero transmission of classical scrapie is also possible.

  12. Evidence of In Utero Transmission of Classical Scrapie in Sheep

    PubMed Central

    Hawkins, Stephen A. C.; Simmons, Marion M.; Bellworthy, Susan J.

    2014-01-01

    Classical scrapie is one of the transmissible spongiform encephalopathies (TSEs), a group of fatal infectious diseases that affect the central nervous system (CNS). Classical scrapie can transmit laterally from ewe to lamb perinatally or between adult animals. Here we report detection of infectivity in tissues of an unborn fetus, providing evidence that in utero transmission of classical scrapie is also possible. PMID:24453368

  13. Predominant involvement of the cerebellum in guinea pigs infected with bovine spongiform encephalopathy (BSE).

    PubMed

    Furuoka, H; Horiuchi, M; Yamakawa, Y; Sata, T

    2011-05-01

    This study reports the experimental transmission of bovine spongiform encephalopathy (BSE) to guinea pigs and describes the cerebellar lesions in these animals. Guinea pigs were inoculated intracerebrally with 10% brain homogenates from BSE-affected cattle. These animals were designated as the first passage. Second and third passages were subsequently performed. All guinea pigs developed infection at each passage. The mean incubation period of the first passage was 370 days post-infection (dpi) and this decreased to 307 dpi and 309 dpi for the second and third passages, respectively. Mild to severe spongiform degeneration and gliosis were observed in the cerebral cortex, thalamus and brainstem. In addition, the affected animals had marked pathological changes in the cerebellum characterized by severe cortical atrophy associated with Bergmann radial gliosis of the molecular layer and reduction in the width of the granular cell layer. Immunohistochemically, intense PrP(Sc) deposition and scattered plaque-like deposits were observed in the molecular and granular cell layers. Cerebellar lesions associated with severe atrophy of the cortex have not been reported in animal prion diseases, including in the experimental transmission of PrP(Sc) to small rodents. These lesions were similar to the lesions of human kuru or the VV2 variant of sporadic Creutzfeldt-Jakob disease, although typical kuru plaques or florid plaques were not observed in the affected animals. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Detection and Localisation of PrPSc in the Liver of Sheep Infected with Scrapie and Bovine Spongiform Encephalopathy

    PubMed Central

    Everest, Sally J.; Ramsay, Andrew M.; Chaplin, Melanie J.; Everitt, Sharon; Stack, Michael J.; Neale, Michael H.; Jeffrey, Martin; Moore, S. Jo; Bellworthy, Susan J.; Terry, Linda A.

    2011-01-01

    Prions are largely contained within the nervous and lymphoid tissue of transmissible spongiform encephalopathy (TSE) infected animals. However, following advances in diagnostic sensitivity, PrPSc, a marker for prion disease, can now be located in a wide range of viscera and body fluids including muscle, saliva, blood, urine and milk, raising concerns that exposure to these materials could contribute to the spread of disease in humans and animals. Previously we demonstrated low levels of infectivity in the liver of sheep experimentally challenged with bovine spongiform encephalopathy. In this study we show that PrPSc accumulated in the liver of 89% of sheep naturally infected with scrapie and 100% of sheep challenged with BSE, at both clinical and preclinical stages of the disease. PrPSc was demonstrated in the absence of obvious inflammatory foci and was restricted to isolated resident cells, most likely Kupffer cells. PMID:21589864

  15. 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.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  17. Spongiform encephalopathy in a herd of greater kudu (Tragelaphus strepsiceros): epidemiological observations.

    PubMed

    Kirkwood, J K; Cunningham, A A; Wells, G A; Wilesmith, J W; Barnett, J E

    1993-10-09

    A small herd of greater kudu, derived from three individuals, has been maintained at the Zoological Society of London since 1970. Spongiform encephalopathy has been diagnosed in five out of eight of the animals born in this herd since 1987. With the possible exception of the first confirmed case, none of these is thought to have been exposed to feeds containing ruminant-derived protein. The pattern of incidence suggests that greater kudu are very susceptible to the disease and that natural lateral transmission may have occurred among them.

  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. Animal models for oral transmission of Listeria monocytogenes

    PubMed Central

    D'Orazio, Sarah E. F.

    2014-01-01

    Listeria monocytogenes has been recognized as a food borne pathogen in humans since the 1980s, but we still understand very little about oral transmission of L. monocytogenes or the host factors that determine susceptibility to gastrointestinal infection, due to the lack of an appropriate small animal model of oral listeriosis. Early feeding trials suggested that many animals were highly resistant to oral infection, and the more reproducible intravenous or intraperitoneal routes of inoculation soon came to be favored. There are a fair number of previously published studies using an oral infection route, but the work varies widely in terms of bacterial strain choice, the methods used for oral transmission, and various manipulations used to enhance infectivity. This mini review summarizes the published literature using oral routes of L. monocytogenes infection and highlights recent technological advances that make oral infection a more attractive model system. PMID:24575393

  20. A model to assess the risk of the introduction into Japan of the bovine spongiform encephalopathy agent through imported animals, meat and meat-and-bone meal.

    PubMed

    Sugiura, K; Ito, K; Yokoyama, R; Kumagai, S; Onodera, T

    2003-12-01

    The authors developed a mathematical model to assess the release risk of the bovine spongiform encephalopathy (BSE) agent into a country through the importation of live cattle, bone-in bovine meat and meat-and-bone meal (MBM) from the United Kingdom and other countries with BSE. Monte Carlo simulation was attempted using this model and input variables. The release risk in Japan, expressed as the weight of infected MBM released in Japan between 1993 and 2000, was estimated to be 23.4 kg to 53.8 kg. The simulation also indicated that imported MBM represented the most important risk factor for releasing the BSE agent into Japan. This paper also provides details of the first five cases of BSE detected in Japan between September 2001 and the end of 2002. In addition, the results of the investigation conducted to determine the source of infection and the measures taken by the Government of Japan to prevent the BSE agent from entering the food and feed chains are also outlined.

  1. 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

  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.

  3. Mechanisms of arthropod transmission of plant and animal viruses.

    PubMed

    Gray, S M; Banerjee, N

    1999-03-01

    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.

  4. 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

  5. Discontools: Identifying gaps in controlling bovine spongiform encephalopathy.

    PubMed

    Simmons, M; Ru, G; Casalone, C; Iulini, B; Cassar, C; Seuberlich, T

    2017-08-10

    This article summarizes the 2016 update of the DISCONTOOLS project gap analysis on bovine spongiform encephalopathy (BSE), which was based on a combination of literature review and expert knowledge. Uncertainty still exists in relation to the pathogenesis, immunology and epidemiology of BSE, but provided that infected material is prohibited from entering the animal feed chain, cases should continue to decline. BSE does not appear to spread between cattle, but if new strains with this ability appear then control would be considerably more difficult. Atypical types of BSE (L-BSE and H-BSE) have been identified, which have different molecular patterns and pathology, and do not display the same clinical signs as classical BSE. Laboratory transmission experiments indicate that the L-BSE agent has zoonotic potential. There is no satisfactory conclusion regarding the origin of the BSE epidemic. C-BSE case numbers declined rapidly following strict controls banning ruminant protein in animal feed, but occasional cases still occur. It is unclear whether these more recent cases indicate inadequate implementation of the bans, or the possibility that C-BSE might occur spontaneously, as has been postulated for H- and L-BSE. All of this will have implications once existing bans and levels of surveillance are both relaxed. Immunochemical tests can only be applied post-mortem. There is no immunological basis for diagnosis in the live animal. All aspects of disease control are expensive, particularly surveillance, specified risk material removal and feed controls. There is pressure to relax feed controls, and concurrent pressure from other sources to reduce surveillance. While the cost benefit argument can be applied successfully to either of these approaches, it would be necessary to maintain the ban on intraspecies recycling and some baseline surveillance. However, the potential risk is not limited to intraspecies recycling; recycling with cross-species transmission may be an

  6. 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

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

    2014-10-17

    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 (PrP(TSE)), 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 (PrP(C)) 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 PrP(TSE) 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. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. 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

  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. 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.

  10. 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

  11. A Mathematical Model of Anthrax Transmission in Animal Populations.

    PubMed

    Saad-Roy, C M; van den Driessche, P; Yakubu, Abdul-Aziz

    2017-02-01

    A general mathematical model of anthrax (caused by Bacillus anthracis) transmission is formulated that includes live animals, infected carcasses and spores in the environment. The basic reproduction number [Formula: see text] is calculated, and existence of a unique endemic equilibrium is established for [Formula: see text] above the threshold value 1. Using data from the literature, elasticity indices for [Formula: see text] and type reproduction numbers are computed to quantify anthrax control measures. Including only herbivorous animals, anthrax is eradicated if [Formula: see text]. For these animals, oscillatory solutions arising from Hopf bifurcations are numerically shown to exist for certain parameter values with [Formula: see text] and to have periodicity as observed from anthrax data. Including carnivores and assuming no disease-related death, anthrax again goes extinct below the threshold. Local stability of the endemic equilibrium is established above the threshold; thus, periodic solutions are not possible for these populations. It is shown numerically that oscillations in spore growth may drive oscillations in animal populations; however, the total number of infected animals remains about the same as with constant spore growth.

  12. 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

  13. A quantitative risk assessment for bovine spongiform encephalopathy in Japan.

    PubMed

    Kadohira, M; Stevenson, M A; Høgåsen, H R; de Koeijer, A

    2012-12-01

    A predictive case-cohort model was applied to Japanese data to analyze the interaction between challenge and stability factors for bovine spongiform encephalopathy (BSE) for the period 1985-2020. BSE risk in cattle was estimated as the expected number of detectable cases per year. The model was comprised of a stochastic spreadsheet calculation model with the following inputs: (1) the origin and quantity of live cattle and meat and bone meal imported into Japan, (2) the age distribution of native cattle, and (3) the estimated annual basic reproduction ratio (R(0) ) for BSE. The estimated probability of having zero detectable cases in Japan in 2015 was 0.90 (95% CI 0.83-0.95). The corresponding value for 2020 was 0.99 (95% CI 0.98-0.99). The model predicted that detectable cases may occur in Japan beyond 2015 because of the assumption that continued transmission was permitted to occur (albeit at a very low level) after the 2001 ban on the importation and domestic use of all processed animal proteins for the production of animal feed and for fertilizer. These results reinforce the need for animal health authorities to monitor the efficacy of control measures so that the future course of the BSE epidemic in Japan can be predicted with greater certainty. © 2012 Society for Risk Analysis.

  14. Transmission of Neospora caninum between wild and domestic animals.

    PubMed

    Gondim, L F P; McAllister, M M; Mateus-Pinilla, N E; Pitt, W C; Mech, L D; Nelson, M E

    2004-12-01

    To determine whether deer can transmit Neospora caninum, brains of naturally infected white-tailed deer (Odocoileus virginianus) were fed to 4 dogs; 2 of these dogs shed oocysts. Oocysts from 1 of the dogs were tested by polymerase chain reaction and found to be positive for N. caninum and negative for Hammondia heydorni. The internal transcribed spacer 1 sequence of the new strain (designated NC-deer1) was identical to N. caninum from domestic animals, indicating that N. caninum is transmitted between wild and domestic animals, often enough to prevent divergent evolution of isolated populations of the parasite. NC-deerl oocysts were administered to a calf that developed a high antibody titer, providing evidence that N. caninum from wildlife can infect cattle. In addition, N. caninum antibody seroprevalence was detected in 64/164 (39%) free-ranging gray wolves (Canis lupus), 12/113 (11%) coyotes (Canis latrans), 50/193 (26%) white-tailed deer, and 8/61 (13%) moose (Alces alces). These data are consistent with a sylvatic transmission cycle of N. caninum between cervids and canids. We speculate that hunting by humans favors the transmission of N. caninum from deer to canids, because deer carcasses are usually eviscerated in the field. Infection of canids in turn increases the risk of transmitting the parasite to domestic livestock.

  15. Highly dynamic animal contact network and implications on disease transmission

    PubMed Central

    Chen, Shi; White, Brad J.; Sanderson, Michael W.; Amrine, David E.; Ilany, Amiyaal; Lanzas, Cristina

    2014-01-01

    Contact patterns among hosts are considered as one of the most critical factors contributing to unequal pathogen transmission. Consequently, networks have been widely applied in infectious disease modeling. However most studies assume static network structure due to lack of accurate observation and appropriate analytic tools. In this study we used high temporal and spatial resolution animal position data to construct a high-resolution contact network relevant to infectious disease transmission. The animal contact network aggregated at hourly level was highly variable and dynamic within and between days, for both network structure (network degree distribution) and individual rank of degree distribution in the network (degree order). We integrated network degree distribution and degree order heterogeneities with a commonly used contact-based, directly transmitted disease model to quantify the effect of these two sources of heterogeneity on the infectious disease dynamics. Four conditions were simulated based on the combination of these two heterogeneities. Simulation results indicated that disease dynamics and individual contribution to new infections varied substantially among these four conditions under both parameter settings. Changes in the contact network had a greater effect on disease dynamics for pathogens with smaller basic reproduction number (i.e. R0 < 2). PMID:24667241

  16. 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 document...

  17. Animal Models for Influenza Virus Pathogenesis and Transmission

    PubMed Central

    Bouvier, Nicole M.; Lowen, Anice C.

    2010-01-01

    Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, and also the virulence of the influenza strain. In humans, the virus is transmitted through either aerosol or contact-based transfer of infectious respiratory secretions. As is evidenced by most zoonotic influenza virus infections, not all strains that can infect humans are able to transmit from person-to-person. Animal models of influenza are essential to research efforts aimed at understanding the viral and host factors that contribute to the disease and transmission outcomes of influenza virus infection in humans. These models furthermore allow the pre-clinical testing of antiviral drugs and vaccines aimed at reducing morbidity and mortality in the population through amelioration of the virulence or transmissibility of influenza viruses. Mice, ferrets, guinea pigs, cotton rats, hamsters and macaques have all been used to study influenza viruses and therapeutics targeting them. Each model presents unique advantages and disadvantages, which will be discussed herein. PMID:21442033

  18. Elevated manganese levels in blood and central nervous system occur before onset of clinical signs in scrapie and bovine spongiform encephalopathy.

    PubMed

    Hesketh, S; Sassoon, J; Knight, R; Hopkins, J; Brown, D R

    2007-06-01

    Prion diseases, or transmissible spongiform encephalopathies, are neurodegenerative diseases that can only be accurately diagnosed by analysis of central nervous system tissue for the presence of an abnormal isoform of the prion protein known as PrP(Sc). Furthermore, these diseases have long incubation periods during which there are no clear symptoms but where the infectious agent could still be present in the tissues. Therefore, the development of diagnostic assays to detect a surrogate marker for the presence of prion disease is essential. Previous studies on mice experimentally infected with scrapie, an ovine spongiform encephalopathy, suggested that changes in the levels of Mn occur in the blood and brain before the onset of symptoms of the disease. To assess whether these findings have relevance to the animal diseases scrapie and bovine spongiform encephalopathy, tissues from bovine spongiform encephalopathy- and scrapie-infected cattle and sheep were analyzed for their metal content and compared with values for noninfected animals. In field cases and experimentally infected animals, elevated Mn was associated with prion infection. Although some central nervous system regions showed elevated Mn, other regions did not. The most consistent finding was an elevation of Mn in blood. This change was present in experimentally infected animals before the onset of symptoms. In scrapie-infected sheep, elevated Mn levels occurred regardless of the genotype of the sheep and were even detected in scrapie-resistant sheep in which no symptoms of disease were detected. These findings suggest that elevated blood Mn could be a potential diagnostic marker for prion infection even in the absence of apparent clinical disease.

  19. Lingering doubts about spongiform encephalopathy and Creutzfeldt-Jakob disease.

    PubMed

    Narang, H K

    2001-07-01

    Bovine spongiform encephalopathy (BSE) is an infectious disease and has been transmitted orally to many other animals, including humans. There is clear evidence of maternal transmission, although disagreement on the source of the BSE agent remains. The current theories link the origin of BSE to common scrapie in sheep. Twenty different strains of the scrapie agent have been isolated from sheep. A search of the literature indicates two distinct clinical syndromes in sheep, both of which have been called scrapie. I have designated these Type I (the common type), which exhibits itchiness and lose their wool, and Type II, which exhibits trembling and ataxia. Sheep inoculated with BSE develop Type II scrapie and they exhibit trembling. When cattle or mink are injected with the Type I strain, only a few will develop a clinical disease. By contrast, no clinical disease has so far been shown in cattle or mink by feeding them with Type I-infected sheep brains. However, either by injecting or feeding with the BSE strain, 100% of calves and mink develop the clinical disease. Evidence suggests that Type II is the cause of BSE. Identical clinical signs of Type II trembling are found in kuru and many of the recent cases of Creutzfeldt-Jakob disease. The BSE agent has caused spongiform encephalopathies (SEs) in domestic cats, tigers, and in some species of ruminants in zoos. The nature of the BSE agent remains unchanged when passaged through a range of species, irrespective of their genetic make up, demonstrating that variations in the host PrP gene are not a major factor in the susceptibility to the BSE agent. Since more than 85 zoo animals of many species have been diagnosed with SEs, from these studies it seems reasonable to conclude that the BSE agent can infect almost all mammalian species, including humans. For eradication of BSE and to reduce the risk of infection to humans, the development of a vaccine against BSE is suggested. Such a possibility should be fully explored.

  20. 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

  1. Bovine spongiform encephalopathy infectivity in greater kudu (Tragelaphus strepsiceros).

    PubMed

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

    2004-06-01

    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.

  2. 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

  3. Properties of L-type bovine spongiform encephalopathy in intraspecies passages.

    PubMed

    Okada, H; Iwamaru, Y; Kakizaki, M; Masujin, K; Imamura, M; Fukuda, S; Matsuura, Y; Shimizu, Y; Kasai, K; Mohri, S; Yokoyama, T

    2012-09-01

    The origin and transmission routes of atypical bovine spongiform encephalopathy (BSE) remain unclear. To assess whether the biological and biochemical characteristics of atypical L-type BSE detected in Japanese cattle (BSE/JP24) are conserved during serial passages within a single host, 3 calves were inoculated intracerebrally with a brain homogenate prepared from first-passaged BSE/JP24-affected cattle. Detailed immunohistochemical and neuropathologic analysis of the brains of second-passaged animals, which had developed the disease and survived for an average of 16 months after inoculation, revealed distribution of spongiform changes and disease-associated prion protein (PrP(Sc)) throughout the brain. Although immunolabeled PrP(Sc) obtained from brain tissue was characterized by the presence of PrP plaques and diffuse synaptic granular accumulations, no stellate-type deposits were detected. Western blot analysis suggested no obvious differences in PrP(Sc) molecular mass or glycoform pattern in the brains of first- and second-passaged cattle. These findings suggest failures to identify differences in mean incubation period and biochemical and neuropathologic properties of the BSE/JP24 prion between the first and second passages in cattle.

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

    PubMed

    Tortosa, Raül; Castells, Xavier; Vidal, Enric; Costa, Carme; Ruiz de Villa, María del Carmen; Sánchez, Alex; Barceló, Anna; Torres, Juan María; Pumarola, Martí; Ariño, Joaquín

    2011-10-28

    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.

  5. Animal-to-Human Transmission of Salmonella Typhimurium DT104A Variant

    PubMed Central

    Orsel, Karin; Wagenaar, Jaap A.; Miko, Angelika; van Duijkeren, Engeline

    2004-01-01

    Salmonella enterica serovar Typhimurium was isolated from a pig, a calf, and a child on a farm in the Netherlands. The isolates were indistinguishable by phenotyping and genotyping methods, which suggests nonfoodborne animal-to-animal and animal-to-human transmission. Persons in close contact with farm animals should be aware of this risk. PMID:15663868

  6. Changes in retinal function and morphology are early clinical signs of disease in cattle with bovine spongiform encephalopathy.

    PubMed

    Greenlee, M Heather West; Smith, Jodi D; Platt, Ekundayo M; Juarez, Jessica R; Timms, Leo L; Greenlee, Justin J

    2015-01-01

    Bovine spongiform encephalopathy (BSE) belongs to a group of fatal, transmissible protein misfolding diseases known as transmissible spongiform encephalopathies (TSEs). All TSEs are caused by accumulation of misfolded prion protein (PrPSc) throughout the central nervous system (CNS), which results in neuronal loss and ultimately death. Like other protein misfolding diseases including Parkinson's disease and Alzheimer's disease, TSEs are generally not diagnosed until the onset of disease after the appearance of unequivocal clinical signs. As such, identification of the earliest clinical signs of disease may facilitate diagnosis. The retina is the most accessible part of the central nervous system, and retinal pathology in TSE affected animals has been previously reported. Here we describe antemortem changes in retinal function and morphology that are detectable in BSE inoculated animals several months (up to 11 months) prior to the appearance of any other signs of clinical disease. We also demonstrate that differences in the severity of these clinical signs reflect the amount of PrPSc accumulation in the retina and the resulting inflammatory response of the tissue. These results are the earliest reported clinical signs associated with TSE infection and provide a basis for understanding the pathology and evaluating therapeutic interventions.

  7. Changes in Retinal Function and Morphology Are Early Clinical Signs of Disease in Cattle with Bovine Spongiform Encephalopathy

    PubMed Central

    West Greenlee, M. Heather; Smith, Jodi D.; Platt, Ekundayo M.; Juarez, Jessica R.; Timms, Leo L.; Greenlee, Justin J.

    2015-01-01

    Bovine spongiform encephalopathy (BSE) belongs to a group of fatal, transmissible protein misfolding diseases known as transmissible spongiform encephalopathies (TSEs). All TSEs are caused by accumulation of misfolded prion protein (PrPSc) throughout the central nervous system (CNS), which results in neuronal loss and ultimately death. Like other protein misfolding diseases including Parkinson’s disease and Alzheimer’s disease, TSEs are generally not diagnosed until the onset of disease after the appearance of unequivocal clinical signs. As such, identification of the earliest clinical signs of disease may facilitate diagnosis. The retina is the most accessible part of the central nervous system, and retinal pathology in TSE affected animals has been previously reported. Here we describe antemortem changes in retinal function and morphology that are detectable in BSE inoculated animals several months (up to 11 months) prior to the appearance of any other signs of clinical disease. We also demonstrate that differences in the severity of these clinical signs reflect the amount of PrPSc accumulation in the retina and the resulting inflammatory response of the tissue. These results are the earliest reported clinical signs associated with TSE infection and provide a basis for understanding the pathology and evaluating therapeutic interventions. PMID:25756286

  8. 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...

  9. 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...

  10. Broad patterns in domestic vector-borne Trypanosoma cruzi transmission dynamics: synanthropic animals and vector control.

    PubMed

    Peterson, Jennifer K; Bartsch, Sarah M; Lee, Bruce Y; Dobson, Andrew P

    2015-10-22

    Chagas disease (caused by Trypanosoma cruzi) is the most important neglected tropical disease (NTD) in Latin America, infecting an estimated 5.7 million people in the 21 countries where it is endemic. It is one of the NTDs targeted for control and elimination by the 2020 London Declaration goals, with the first goal being to interrupt intra-domiciliary vector-borne T. cruzi transmission. A key question in domestic T. cruzi transmission is the role that synanthropic animals play in T. cruzi transmission to humans. Here, we ask, (1) do synanthropic animals need to be targeted in Chagas disease prevention policies?, and (2) how does the presence of animals affect the efficacy of vector control? We developed a simple mathematical model to simulate domestic vector-borne T. cruzi transmission and to specifically examine the interaction between the presence of synanthropic animals and effects of vector control. We used the model to explore how the interactions between triatomine bugs, humans and animals impact the number and proportion of T. cruzi-infected bugs and humans. We then examined how T. cruzi dynamics change when control measures targeting vector abundance are introduced into the system. We found that the presence of synanthropic animals slows the speed of T. cruzi transmission to humans, and increases the sensitivity of T. cruzi transmission dynamics to vector control measures at comparable triatomine carrying capacities. However, T. cruzi transmission is amplified when triatomine carrying capacity increases with the abundance of syntathoropic hosts. Our results suggest that in domestic T. cruzi transmission scenarios where no vector control measures are in place, a reduction in synanthropic animals may slow T. cruzi transmission to humans, but it would not completely eliminate transmission. To reach the 2020 goal of interrupting intra-domiciliary T. cruzi transmission, it is critical to target vector populations. Additionally, where vector control measures

  11. Spongiform Encephalopathy in a Miniature Zebu

    PubMed Central

    Botteron, Catherine; Wenker, Christian; Café-Marçal, Valeria; Oevermann, Anna; Haase, Bianca; Leeb, Tosso; Heim, Dagmar; Zurbriggen, Andreas

    2006-01-01

    The first case of spongiform encephalopathy in a zebu (Bos indicus) was identified in a zoo in Switzerland. Although histopathologic and immunohistochemical analyses of the central nervous system indicated a diagnosis of bovine spongiform encephalopathy (BSE), molecular typing showed some features different from those of BSE in cattle (B. taurus). PMID:17326950

  12. Multilevel animal societies can emerge from cultural transmission.

    PubMed

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

    2015-09-08

    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.

  13. 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

  14. Transmission of Neospora caninum between wild and domestic animals

    USGS Publications Warehouse

    Gondim, L.F.P.; McAllister, M.M.; Mateus-Pinilla, N. E.; Pitt, W.; Mech, L.D.; Nelson, M.E.; Lenarz, M.S.

    2004-01-01

    Neospora caninum is a protozoan parasite that can cause abortions in cows. N. caninum antibody seroprevalence was detected in 64/164 (39%) free-ranging gray wolves from Minnesota, 30/150 (20%) white-tailed deer, and 8/61 (13%) moose. These data are consistent with a sylvatic transmission cycle of N. caninum between cervids and canids. Infection of canids increases the risk of transmitting the parasite to domestic livestock.

  15. Transmission line based thermoacoustic imaging of small animals

    NASA Astrophysics Data System (ADS)

    Omar, Murad; Kellnberger, Stephan; Sergiadis, George; Razansky, Daniel; Ntziachristos, Vasilis

    2013-06-01

    We have generated high resolution images of RF-Contrast in small animals using nearfield thermoacoustic system. This enables us to see some anatomical features of a mouse such as the heart, the spine and the boundary. OCIS codes: (000.0000) General; (000.0000) General [8-pt. type. For codes, see www.opticsinfobase.org/submit/ocis.

  16. 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

  17. High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals

    DTIC Science & Technology

    2004-07-01

    inhibitors of prp(exp sc) accumulation in scrapie -infected mouse neuroblastoma cells (ScN2a) also have anti- scrapie activity in rodents. To expedite the...format. A library of 2000 drugs and natural products was screened in ScN2a cells infected with RML (Chandler) or 22L scrapie strains. Seventeen had IC

  18. High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals

    DTIC Science & Technology

    2007-07-01

    and cause it to cluster and be internalized from the surface of cultured cells. In consideration of these and other observations, we developed a new...Several different classes of TSE inhibitors share structural similarities, compete for the same site(s) on PrPC, and induce the clustering and...many protein aggregation diseases, smaller nonfibrillar oligomers are more pathological than large fibrils or clusters of fibrils (plaques

  19. High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals

    DTIC Science & Technology

    2006-07-01

    porphyrin, iron tetrasulfonatophenyl porphine, was found to have prophylactic activity as well as therapeutic activity. When treatment of this porphyrin...Found that iron tetrasulfonatophenyl porphine has therapeutic anti-scrapie activity in mice. Treatment started two weeks after inoculation of...Invited Presentations: “New compounds for the treatment of prion diseases.” CJD Foundation Family Conference, July 2005. Washington, DC

  20. High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals

    DTIC Science & Technology

    2008-07-01

    its relatively low toxicity and use as a human food. Finally, tetrandrine, a Chinese herbal medicine with anti-malarial activity, was tested. Generally...apoptosis of cerebellar granule cells in transgenic mice expressing a PrP insertional mutation. Proc. Natl Acad. Sci. USA 97, 5574–5579 (2000). 45

  1. Intranasal immunization with an adenovirus vaccine protects guinea pigs from Ebola virus transmission by infected animals.

    PubMed

    Wong, Gary; Richardson, Jason S; Cutts, Todd; Qiu, Xiangguo; Kobinger, Gary P

    2015-04-01

    Experimental Ebola virus (EBOV) vaccines have previously been shown to protect animals against a high dose intramuscular (IM) challenge, which is seen as a stringent challenge model. However, the protective efficacy against other modes of infection, such as contact with infectious hosts, is unknown. Using a previously established EBOV transmission animal model, we evaluated the efficacy of an adenovirus-based EBOV vaccine given to guinea pigs (gps) 4weeks before direct contact with untreated, infectious animals. Prior vaccination resulted in robust levels of EBOV-specific antibodies and conferred complete protection in gps. These results support the use of vaccines to prevent EBOV transmission between hosts.

  2. Animal Model Reveals Potential Waterborne Transmission of Helicobacter pylori Infection.

    PubMed

    Boehnke, Kevin F; Eaton, Kathryn A; Valdivieso, Manuel; Baker, Laurence H; Xi, Chuanwu

    2015-10-01

    Helicobacter pylori infection has been consistently associated with lack of access to clean water and proper sanitation, but no studies have demonstrated that the transmission of H. pylori can occur from drinking contaminated water. In this study, we used a laboratory mouse model to test whether waterborne H. pylori could cause gastric infection. Groups of immunocompetent C57/BL6 Helicobacter-free mice were exposed to static concentrations (1.29 × 10(5), 10(6), 10(7), 10(8), and 10(9) CFU/L) of H. pylori in their drinking water for 4 weeks. One group of Helicobacter-free mice was exposed to uncontaminated water as a negative control. H. pylori morphology changes in water were examined using microscopy Live/Dead staining. Following exposure, H. pylori infection and inflammation status in the stomach were evaluated using quantitative culture, PCR, the rapid urease test, and histology. None of the mice in the negative control or 10(5) groups were infected. One of 20 cages (one of 40 mice) of the 10(6) group, three of 19 cages (four of 38 mice) of the 10(7) CFU/L group, 19 of 20 cages (33 of 40 mice) of the 10(8) group, and 20 of 20 cages (39 of 40 mice) of the 10(9) CFU/L group were infected. Infected mice had significantly higher gastric inflammation than uninfected mice (27.86% higher inflammation, p < .0001). We offer proof that H. pylori in water is infectious in mice, suggesting that humans drinking contaminated water may be at risk of contracting H. pylori infection. Much work needs to be performed to better understand the risk of infection from drinking H. pylori-contaminated water. © 2015 John Wiley & Sons Ltd.

  3. Mathematical Models for Estimating the Risks of Bovine Spongiform Encephalopathy (BSE).

    PubMed

    Al-Zoughool, Mustafa; Cottrell, David; Elsaadany, Susie; Murray, Noel; Oraby, Tamer; Smith, Robert; Krewski, Daniel

    2015-01-01

    When the bovine spongiform encephalopathy (BSE) epidemic first emerged in the United Kingdom in the mid 1980s, the etiology of animal prion diseases was largely unknown. Risk management efforts to control the disease were also subject to uncertainties regarding the extent of BSE infections and future course of the epidemic. As understanding of BSE increased, mathematical models were developed to estimate risk of BSE infection and to predict reductions in risk in response to BSE control measures. Risk models of BSE-transmission dynamics determined disease persistence in cattle herds and relative infectivity of cattle prior to onset of clinical disease. These BSE models helped in understanding key epidemiological features of BSE transmission and dynamics, such as incubation period distribution and age-dependent infection susceptibility to infection with the BSE agent. This review summarizes different mathematical models and methods that have been used to estimate risk of BSE, and discusses how such risk projection models have informed risk assessment and management of BSE. This review also provides some general insights on how mathematical models of the type discussed here may be used to estimate risks of emerging zoonotic diseases when biological data on transmission of the etiological agent are limited.

  4. Aquaporin 1 and aquaporin 4 overexpression in bovine spongiform encephalopathy in a transgenic murine model and in cattle field cases.

    PubMed

    Costa, Carme; Tortosa, Raül; Rodríguez, Agustín; Ferrer, Isidre; Torres, Juan Maria; Bassols, Anna; Pumarola, Martí

    2007-10-17

    Aquaporins (AQP) are a family of transmembrane proteins that act as water selective channels. AQP1 and AQP4 are widely expressed in the central nervous system where they play several roles. Overexpression of AQP has been reported in some human and animal transmissible spongiform encephalopathies, but information is scanty about their distribution in the central nervous system in bovine spongiform encephalopathy (BSE). Double immunohistochemistry for AQP1, AQP4 and GFAP was developed in a transgenic mouse line overexpressing the bovine cellular prion protein (BoTg110), intracerebrally infected with cattle BSE. Western blot for AQP1 and AQP4, and immunohistochemistry for both AQP and GFAP were carried out in cases of BSE-diagnosed cattle as part of surveillance plan in Catalonia (Spain). A marked increase in AQP1 and AQP4 was observed in mice at the terminal stage of the disease, when they had a wide range of clinical signs, whereas no increase could be observed in the early stage before the onset of the clinical signs. In cattle which did not show evidence of clinical signs, both AQP already showed a great increase. The AQP overexpression correlated with GFAP-immunoreactive astrocytes and PrPres deposition in both cases. The results of this study suggest that AQP overexpression in glial cells could lead to an imbalance in water and ion homeostasis which could contribute to triggering the typical histopathological changes of BSE.

  5. Transcytosis of murine-adapted bovine spongiform encephalopathy agents in an in vitro bovine M cell model.

    PubMed

    Miyazawa, Kohtaro; Kanaya, Takashi; Takakura, Ikuro; Tanaka, Sachi; Hondo, Tetsuya; Watanabe, Hitoshi; Rose, Michael T; Kitazawa, Haruki; Yamaguchi, Takahiro; Katamine, Shigeru; Nishida, Noriyuki; Aso, Hisashi

    2010-12-01

    Transmissible spongiform encephalopathies (TSE), including bovine spongiform encephalopathy (BSE), are fatal neurodegenerative disorders in humans and animals. BSE appears to have spread to cattle through the consumption of feed contaminated with BSE/scrapie agents. In the case of an oral infection, the agents have to cross the gut-epithelial barrier. We recently established a bovine intestinal epithelial cell line (BIE cells) that can differentiate into the M cell type in vitro after lymphocytic stimulation (K. Miyazawa, T. Hondo, T. Kanaya, S. Tanaka, I. Takakura, W. Itani, M. T. Rose, H. Kitazawa, T. Yamaguchi, and H. Aso, Histochem. Cell Biol. 133:125-134, 2010). In this study, we evaluated the role of M cells in the intestinal invasion of the murine-adapted BSE (mBSE) agent using our in vitro bovine intestinal epithelial model. We demonstrate here that M cell-differentiated BIE cells are able to transport the mBSE agent without inactivation at least 30-fold more efficiently than undifferentiated BIE cells in our in vitro model. As M cells in the follicle-associated epithelium are known to have a high ability to transport a variety of macromolecules, viruses, and bacteria from gut lumen to mucosal immune cells, our results indicate the possibility that bovine M cells are able to deliver agents of TSE, not just the mBSE agent.

  6. Transcytosis of Murine-Adapted Bovine Spongiform Encephalopathy Agents in an In Vitro Bovine M Cell Model▿ † #

    PubMed Central

    Miyazawa, Kohtaro; Kanaya, Takashi; Takakura, Ikuro; Tanaka, Sachi; Hondo, Tetsuya; Watanabe, Hitoshi; Rose, Michael T.; Kitazawa, Haruki; Yamaguchi, Takahiro; Katamine, Shigeru; Nishida, Noriyuki; Aso, Hisashi

    2010-01-01

    Transmissible spongiform encephalopathies (TSE), including bovine spongiform encephalopathy (BSE), are fatal neurodegenerative disorders in humans and animals. BSE appears to have spread to cattle through the consumption of feed contaminated with BSE/scrapie agents. In the case of an oral infection, the agents have to cross the gut-epithelial barrier. We recently established a bovine intestinal epithelial cell line (BIE cells) that can differentiate into the M cell type in vitro after lymphocytic stimulation (K. Miyazawa, T. Hondo, T. Kanaya, S. Tanaka, I. Takakura, W. Itani, M. T. Rose, H. Kitazawa, T. Yamaguchi, and H. Aso, Histochem. Cell Biol. 133:125-134, 2010). In this study, we evaluated the role of M cells in the intestinal invasion of the murine-adapted BSE (mBSE) agent using our in vitro bovine intestinal epithelial model. We demonstrate here that M cell-differentiated BIE cells are able to transport the mBSE agent without inactivation at least 30-fold more efficiently than undifferentiated BIE cells in our in vitro model. As M cells in the follicle-associated epithelium are known to have a high ability to transport a variety of macromolecules, viruses, and bacteria from gut lumen to mucosal immune cells, our results indicate the possibility that bovine M cells are able to deliver agents of TSE, not just the mBSE agent. PMID:20861256

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

    NASA Astrophysics Data System (ADS)

    Halloran, Siobhan; Ristenpart, William

    2013-11-01

    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 pathogen transmission between the animals, to date the infectious disease community has paid little attention to the effect of airspeed or turbulent 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 an axial fan, thus mimicking the release and transport of expiratory aerosols exhaled by an inoculated animal. We show that for fan-generated turbulence the plume width is invariant with the mean airspeed and, close to the point source, increases linearly with downstream position. Importantly, the turbulent dispersivity is insensitive to the presence of meshes placed downstream from the point source, indicating that the fan length scale dictates the turbulent intensity and corresponding dispersivity.

  9. Zoonotic Hepatitis E Virus: Classification, Animal Reservoirs and Transmission Routes.

    PubMed

    Doceul, Virginie; Bagdassarian, Eugénie; Demange, Antonin; Pavio, Nicole

    2016-10-03

    During the past ten years, several new hepatitis E viruses (HEVs) have been identified in various animal species. In parallel, the number of reports of autochthonous hepatitis E in Western countries has increased as well, raising the question of what role these possible animal reservoirs play in human infections. The aim of this review is to present the recent discoveries of animal HEVs and their classification within the Hepeviridae family, their zoonotic and species barrier crossing potential, and possible use as models to study hepatitis E pathogenesis. Lastly, this review describes the transmission pathways identified from animal sources.

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

    PubMed

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

    2015-09-01

    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 PrP(C) 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 PrP(C) and measured the time required for conversion to the amyloid (PrP(Res)) 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. 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 showed that

  11. 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

  12. Bovine spongiform encephalopathy surveillance in the Republic of Korea.

    PubMed

    Lee, Y H; Kim, M J; Tark, D S; Sohn, H J; Yun, E I; Cho, I S; Choi, Y P; Kim, C L; Lee, J H; Kweon, C H; Joo, Y S; Chung, G S; Lee, J H

    2012-12-01

    National surveillance for bovine spongiform encephalopathy (BSE) began in the Republic of Korea (ROK) in 1996. Surveillance programmes changed overtime to comply with the guidelines of the World Organisation for Animal Health (OIE). Bovine spongiform encephalopathy was designated as a notifiable disease in 1997. From July 2008, the BSE surveillance programme was intensified to test cattle in designated high-risk populations more effectively. New measures included the compulsory testing of all non-ambulatory cattle at abattoirs, and encouraging the testing of all dead cattle examined and recorded under the Mutual Aid Insurance Scheme (fallen stock). In addition, there was a vigorous search for animals suspected of being clinically infected. As a result, a total of 426,919 OIE points were achieved over a period of seven consecutive years to the end of October 2009. This enabled the submission of a successful application to the OIE in 2010 for recognition of the ROK's BSE disease status as being one of controlled risk, in accordance with Chapter 11.5. of the OIE Terrestrial Animal Health Code.

  13. Transient Fecal Shedding and Limited Animal-to-Animal Transmission of Clostridium difficile by Naturally Infected Finishing Feedlot Cattle ▿

    PubMed Central

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

    2011-01-01

    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

  14. 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.

  15. Monkeypox Disease Transmission in an Experimental Setting: Prairie Dog Animal Model

    PubMed Central

    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

  16. Transmission of Coxiella burnetii to cage mates using murine animal model.

    PubMed

    Bechah, Yassina; Raoult, Didier

    2017-02-01

    Aerosols from the products of abortions of infected animals with Coxiella burnetii were known to be the main source of infection in humans with this bacterium. However, little is known about the excretion of C. burnetii in the feces and urine of infected mice, or the dynamic of transmission between infected and healthy mice. To investigate whether C. burnetii can be excreted in the feces and urine of infected mice and whether transmission to uninfected cage mates occurs, male mice were inoculated with C. burnetii using a "whole body aerosol system" and feces and urine were collected different time points post-infection from these mice. One hour post exposure to aerosols, uninfected mice was placed with infected mice and the transmission was monitored using blood, and organs biopsies collected after sacrifice of contact mice different time points post-contact. Bacterial DNA was not detected in the feces and urine of infected mice at 3, 7, 14 and 28days post-inoculation suggesting that C. burnetii was not excreted in the feces and urine and consequently they cannot be source of contamination. However, based on the positive PCR results for lungs, blood, spleen, tracheal lymph nodes and cervical lymph nodes, some of the contact animals were considered contaminated at 8days post-contact. These results indicated that transmission of C. burnetii to contact animals occurs, and it is unlikely that feces and urine act as source of this transmission. Further experiments are needed to clarify the exact mode of contamination.

  17. Transmission of MRSA between companion animals and infected human patients presenting to outpatient medical care facilities.

    PubMed

    Ferreira, Jorge Pinto; Anderson, Kevin L; Correa, Maria T; Lyman, Roberta; Ruffin, Felicia; Reller, L Barth; Fowler, Vance G

    2011-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in both human and veterinary medicine. The importance of companion animals as reservoirs of human infections is currently unknown. The companion animals of 49 MRSA-infected outpatients (cases) were screened for MRSA carriage, and their bacterial isolates were compared with those of the infected patients using Pulsed-Field Gel Electrophoresis (PFGE). Rates of MRSA among the companion animals of MRSA-infected patients were compared to rates of MRSA among companion animals of pet guardians attending a "veterinary wellness clinic" (controls). MRSA was isolated from at least one companion animal in 4/49 (8.2%) households of MRSA-infected outpatients vs. none of the pets of the 50 uninfected human controls. Using PFGE, patient-pets MRSA isolates were identical for three pairs and discordant for one pair (suggested MRSA inter-specie transmission p-value = 0.1175). These results suggest that companion animals of MRSA-infected patients can be culture-positive for MRSA, representing a potential source of infection or re-infection for humans. Further studies are required to better understand the epidemiology of MRSA human-animal inter-specie transmission.

  18. Design and analysis of small-scale transmission experiments with animals.

    PubMed

    Velthuis, A G J; Bouma, A; Katsma, W E A; Nodelijk, G; De Jong, M C M

    2007-02-01

    Interactions between pathogens and hosts at the population level should be considered when studying the effectiveness of control measures for infectious diseases. The advantage of doing transmission experiments compared to field studies is that they offer a controlled environment in which the effect of a single factor can be investigated, while variation due to other factors is minimized. This paper gives an overview of the biological and mathematical aspects, bottlenecks and solutions of developing and executing transmission experiments with animals. Different methods of analysis and different experimental designs are discussed. Final size methods are often used for analysing transmission data, but have never been published in a refereed journal; therefore, they will be described in detail in this paper. We hope that this information is helpful for scientists who are considering performing transmission experiments.

  19. 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

  20. An outbreak of canine distemper virus in tigers (Panthera tigris): possible transmission from wild animals to zoo animals.

    PubMed

    Nagao, Yumiko; Nishio, Yohei; Shiomoda, Hiroshi; Tamaru, Seiji; Shimojima, Masayuki; Goto, Megumi; Une, Yumi; Sato, Azusa; Ikebe, Yusuke; Maeda, Ken

    2012-06-01

    Canine distemper virus (CDV), a morbillivirus that causes one of the most contagious and lethal viral diseases known in canids, has an expanding host range, including wild animals. Since December 2009, several dead or dying wild raccoon dogs (Nyctereutes procyonoides) were found in and around one safari-style zoo in Japan, and CDV was isolated from four of these animals. In the subsequent months (January to February 2010), 12 tigers (Panthera tigris) in the zoo developed respiratory and gastrointestinal diseases, and CDV RNA was detected in fecal samples of the examined tigers. In March 2010, one of the tigers developed a neurological disorder and died; CDV was isolated from the lung of this animal. Sequence analysis of the complete hemagglutinin (H) gene and the signal peptide region of the fusion (F) gene showed high homology among these isolates (99.8-100%), indicating that CDV might have been transmitted from raccoon dog to tiger. In addition, these isolates belonged to genotype Asia-1 and had lower homology (<90%) to the vaccine strain (Onderstepoort). Seropositivity of lions (Panthera leo) in the zoo and wild bears (Ursus thibetanus) captured around this area supported the theory that a CDV epidemic had occurred in many mammal species in and around the zoo. These results indicate a risk of CDV transmission among many animal species, including large felids and endangered species.

  1. The significant but understudied impact of pathogen transmission from humans to animals.

    PubMed

    Epstein, Jonathan H; Price, Joan T

    2009-10-01

    Zooanthroponotic pathogens, which are transmitted from humans to nonhuman animals, are an understudied aspect of global health, despite their potential to cause significant disease burden in wild and domestic animal populations and affect global economies. Some key human-borne pathogens that have been shown to infect animals and cause morbidity and mortality include measles virus (paramyxoviruses), influenza A virus (orthomyxoviruses), herpes simplex 1 virus (herpesviruses), protozoal and helminthic parasites, and bacteria such as methicillin-resistant Staphylococcus aureus and Mycobacterium tuberculosis. However, zooanthroponotic pathogens are most commonly reported in captive animals or domestic livestock with close human contact; there, the potential for economic loss and human reinfection is most apparent. There is also the potential for infection in wild animal populations, which may threaten endangered species and decrease biodiversity. The emergence and reemergence of human-borne pathogens in wildlife may also have negative consequences for human health if these pathogens cycle back into humans. Many of the anthropogenic drivers of zoonotic disease emergence also facilitate zooanthroponotic transmission. Increasing research to better understand the occurrence of and the potential for bidirectional pathogen transmission between humans and animals is essential for improving global health. Mt Sinai J Med 76:448-455, 2009. (c) 2009 Mount Sinai School of Medicine.

  2. 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.

  3. Prioritization of Companion Animal Transmissible Diseases for Policy Intervention in Europe.

    PubMed

    Cito, F; Rijks, J; Rantsios, A T; Cunningham, A A; Baneth, G; Guardabassi, L; Kuiken, T; Giovannini, A

    2016-07-01

    A number of papers have been published on the prioritization of transmissible diseases in farm animals and wildlife, based either on semiquantitative or truly quantitative methods, but there is no published literature on the prioritization of transmissible diseases in companion animals. In this study, available epidemiological data for diseases transmissible from companion animals to man were analysed with the aim of developing a procedure suitable for their prioritization within a European framework. A new method and its associated questionnaire and scoring system were designed based on methods described by the World Organisation for Animal Health (OIE). Modifications were applied to allow for the paucity of specific information on companion animal transmissible diseases. The OIE method was also adapted to the subject and to the regional scope of the interprofessional network addressing zoonotic diseases transmitted via companion animals in Europe: the Companion Animals multisectoriaL interprofessionaL Interdisciplinary Strategic Think tank On zoonoses (CALLISTO). Adaptations were made based on information collected from expert groups on viral, bacterial and parasitic diseases using a structured questionnaire, in which all questions were closed-ended. The expert groups were asked to select the most appropriate answer for each question taking into account the relevance and reliability of the data available in the scientific literature. Subsequently, the scoring of the answers obtained for each disease covered by the questionnaire was analysed to obtain two final overall scores, one for human health impact and one for agricultural economic impact. The adapted method was then applied to select the 15 most important pathogens (five for each pathogen group: viral, bacterial and parasitic) on the basis of their overall impact on public health and agriculture. The result of the prioritization exercise was a joint priority list (available at www.callistoproject.eu) of

  4. Analysis of gene expression in white blood cells of cattle orally challenged with bovine amyloidotic spongiform encephalopathy.

    PubMed

    Panelli, Simona; Strozzi, Francesco; Capoferri, Rossana; Barbieri, Ilaria; Martinelli, Nicola; Capucci, Lorenzo; Lombardi, Guerino; Williams, John L

    2011-01-01

    Bovine amyloidotic spongiform encephalopathy (BASE) is one of the recently discovered atypical forms of BSE, which is transmissible to primates, and may be the bovine equivalent of sporadic Creutzfeldt-Jacob disease (CJD) in humans. Although it is transmissible, it is unknown whether BASE is acquired through infection or arises spontaneously. In the present study, the gene expression of white blood cells (WBCs) from 5 cattle at 1 yr after oral BASE challenge was compared with negative controls using a custom microarray containing 43,768 unique gene probes. In total, 56 genes were found to be differentially expressed between BASE and control animals with a log fold change of 2 or greater. Of these, 39 were upregulated in BASE animals, while 17 were downregulated. The majority of these genes are related to immune function. In particular, BASE animals appeared to have significantly modified expression of genes linked to T- and B-cell development and activation, and to inflammatory responses. The potential impacts of these gene expression changes are described.

  5. 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

  6. Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy.

    PubMed

    Okada, Hiroyuki; Masujin, Kentaro; Miyazawa, Kohtaro; Iwamaru, Yoshihumi; Imamura, Morikazu; Matsuura, Yuichi; Arai, Shozo; Fukuda, Shigeo; Murayama, Yuichi; Yokoyama, Takashi

    2017-01-01

    H-type bovine spongiform encephalopathy (H-BSE) is an atypical form of BSE in cattle. During passaging of H-BSE in transgenic bovinized (TgBoPrP) mice, a novel phenotype of BSE, termed BSE-SW emerged and was characterized by a short incubation time and host weight loss. To investigate the biological and biochemical properties of the BSE-SW prion, a transmission study was conducted in cattle, which were inoculated intracerebrally with brain homogenate from BSE-SW-infected TgBoPrP mice. The disease incubation period was approximately 15 months. The animals showed characteristic neurological signs of dullness, and severe spongiform changes and a widespread, uniform distribution of disease-associated prion protein (PrP(Sc)) were observed throughout the brain of infected cattle. Immunohistochemical PrP(Sc) staining of the brain revealed the presence of intraglial accumulations and plaque-like deposits. No remarkable differences were identified in vacuolar lesion scores, topographical distribution patterns, and staining types of PrP(Sc) in the brains of BSE-SW- vs H-BSE-infected cattle. PrP(Sc) deposition was detected in the ganglia, vagus nerve, spinal nerve, cauda equina, adrenal medulla, and ocular muscle. Western blot analysis revealed that the specific biochemical properties of the BSE-SW prion, with an additional 10- to 12-kDa fragment, were well maintained after transmission. These findings indicated that the BSE-SW prion has biochemical properties distinct from those of H-BSE in cattle, although clinical and pathologic features of BSW-SW in cattle are indistinguishable from those of H-BSE. The results suggest that the 2 infectious agents, BSE-SW and H-BSE, are closely related strains.

  7. Sheep-passaged bovine spongiform encephalopathy agent exhibits altered pathobiological properties in bovine-PrP transgenic mice.

    PubMed

    Espinosa, Juan Carlos; Andréoletti, Olivier; Castilla, Joaquín; Herva, María Eugenia; Morales, Mónica; Alamillo, Elia; San-Segundo, Fayna Díaz; Lacroux, Caroline; Lugan, Séverine; Salguero, Francisco Javier; Langeveld, Jan; Torres, Juan María

    2007-01-01

    Sheep can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern. In this study, the transmission in BoPrP-Tg110 mice of prions from BSE-infected sheep was examined and compared to the transmission of original cattle BSE in cattle and sheep scrapie prions. Our results indicate no transmission barrier for sheep BSE prions to infect BoPrP-Tg110 mice, but the course of the disease is accelerated compared to the effects of the original BSE isolate. The shortened incubation period of sheep BSE in the model was conserved in subsequent passage in BoPrP-Tg110 mice, indicating that it is not related to infectious titer differences. Biochemical signature, lesion profile, and PrP(Sc) deposition pattern of both cattle and sheep BSE were similar. In contrast, all three sheep scrapie isolates tested showed an evident transmission barrier and further adaptation in subsequent passage. Taken together, those data indicate that BSE agent can be altered by crossing a species barrier, raising concerns about the virulence of this new prion towards other species, including humans. The BoPrP-Tg110 mouse bioassay should be considered as a valuable tool for discriminating scrapie and BSE in sheep.

  8. Tolerance of infection: A role for animal behavior, potential immune mechanisms, and consequences for parasite transmission.

    PubMed

    Adelman, James S; Hawley, Dana M

    2017-02-01

    Infected organisms can resist or tolerate infection, with tolerance of infection defined as minimizing per-parasite reductions in fitness. Although tolerance is well studied in plants, researchers have only begun to probe the mechanisms and transmission consequences of tolerance in animals. Here we suggest that research on tolerance in animals would benefit from explicitly incorporating behavior as a component of tolerance, given the importance of behavior for host fitness and parasite transmission. We propose two distinct manifestations of tolerance in animals: tissue-specific tolerance, which minimizes fitness losses due to tissue damage during infection, and behavioral tolerance, which minimizes fitness losses by maintaining normal, fitness-enhancing behaviors during infection. Here we briefly review one set of potential immune mechanisms underlying both responses in vertebrate animals: inflammation and its associated signaling molecules. Inflammatory responses, including broadly effective resistance mechanisms like the production of reactive oxygen species, can incur severe costs in terms of damage to a host's own tissues, thereby reducing tissue-specific tolerance. In addition, signaling molecules involved in these responses facilitate stereotypical behavioral changes during infection, which include lethargy and anorexia, reducing normal behaviors and behavioral tolerance. We consider how tissue-specific and behavioral tolerance may vary independently or in conjunction and outline potential consequences of such covariation for the transmission of infectious diseases. We put forward the distinction between tissue-specific and behavioral tolerance not as a definitive framework, but to help stimulate and broaden future research by considering animal behavior as intimately linked to the mechanisms and consequences of tolerance in animals. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. One Health and Food-Borne Disease: Salmonella Transmission between Humans, Animals, and Plants.

    PubMed

    Silva, Claudia; Calva, Edmundo; Maloy, Stanley

    2014-02-01

    There are >2,600 recognized serovars of Salmonella enterica. Many of these Salmonella serovars have a broad host range and can infect a wide variety of animals, including mammals, birds, reptiles, amphibians, fish, and insects. In addition, Salmonella can grow in plants and can survive in protozoa, soil, and water. Hence, broad-host-range Salmonella can be transmitted via feces from wild animals, farm animals, and pets or by consumption of a wide variety of common foods: poultry, beef, pork, eggs, milk, fruit, vegetables, spices, and nuts. Broad-host-range Salmonella pathogens typically cause gastroenteritis in humans. Some Salmonella serovars have a more restricted host range that is associated with changes in the virulence plasmid pSV, accumulation of pseudogenes, and chromosome rearrangements. These changes in host-restricted Salmonella alter pathogen-host interactions such that host-restricted Salmonella organisms commonly cause systemic infections and are transmitted between host populations by asymptomatic carriers. The secondary consequences of efforts to eliminate host-restricted Salmonella serovars demonstrate that basic ecological principles govern the environmental niches occupied by these pathogens, making it impossible to thwart Salmonella infections without a clear understanding of the human, animal, and environmental reservoirs of these pathogens. Thus, transmission of S. enterica provides a compelling example of the One Health paradigm because reducing human infections will require the reduction of Salmonella in animals and limitation of transmission from the environment.

  10. Transmission of MRSA between humans and animals on duck and turkey farms.

    PubMed

    van Duijkeren, E; Hengeveld, P; Zomer, T P; Landman, F; Bosch, T; Haenen, A; van de Giessen, A

    2016-01-01

    The objectives of this study were to estimate the prevalence of MRSA on duck and turkey farms, identify risk factors for human carriage and study transmission between animals and humans. On 10 duck and 10 turkey farms, samples were taken from animals, poultry houses, home residences and humans and cultured using pre-enrichment and selective enrichment. MRSA isolates were typed by spa typing and multiple-locus variable number tandem repeat analysis (MLVA) typing. A subset of isolates from animals and humans was investigated using whole-genome mapping. MRSA was found on one duck farm and three turkey farms. On duck farms, all humans were MRSA negative. On turkey farms, 5 of 11 farmers, 2 of 32 family members and 15 of 49 samples from the home residences were MRSA positive. Individuals with daily contact with turkeys were significantly more often MRSA positive than individuals without daily contact. All MRSA isolates belonged to livestock-associated MLVA complex 398, belonged to spa type t011, were negative for Panton-Valentine leucocidin, were mecC negative and were mecA positive. Whole-genome mapping proved a valuable tool to study the transmission of livestock-associated MRSA and showed that on two turkey farms the isolates from the animals and humans were indistinguishable or closely related, indicating transmission. MRSA carriage in individuals in daily contact with turkeys was significantly higher than that in individuals only living on the farms or than in the general Dutch population. Therefore, persons with a high degree of contact with turkeys have an increased risk of MRSA carriage, and we propose that they should be screened prior to hospitalization in order to decrease the risk of nosocomial transmission. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. 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.

  12. Experimental classical bovine spongiform encephalopathy: definition and progression of neural PrP immunolabeling in relation to diagnosis and disease controls.

    PubMed

    Simmons, M M; Spiropoulos, J; Webb, P R; Spencer, Y I; Czub, S; Mueller, R; Davis, A; Arnold, M E; Marsh, S; Hawkins, S A C; Cooper, J A; Konold, T; Wells, G A H

    2011-09-01

    Tissues from sequential-kill time course studies of bovine spongiform encephalopathy (BSE) were examined to define PrP immunohistochemical labeling forms and map disease-specific labeling over the disease course after oral exposure to the BSE agent at two dose levels. Study was confined to brainstem, spinal cord, and certain peripheral nervous system ganglia-tissues implicated in pathogenesis and diagnosis or disease control strategies. Disease-specific labeling in the brainstem in 39 of 220 test animals showed the forms and patterns observed in natural disease and invariably preceded spongiform changes. A precise temporal pattern of increase in labeling was not apparent, but labeling was generally most widespread in clinical cases, and it always involved neuroanatomic locations in the medulla oblongata. In two cases, sparse labeling was confined to one or more neuroanatomic nuclei of the medulla oblongata. When involved, the spinal cord was affected at all levels, providing no indication of temporal spread within the cord axis or relative to the brainstem. Where minimal PrP labeling occurred in the thoracic spinal cord, it was consistent with initial involvement of general visceral efferent neurons. Labeling of ganglia involved only sensory ganglia and only when PrP was present in the brainstem and spinal cord. These experimental transmissions mimicked the neuropathologic findings in BSE-C field cases, independent of dose of agent or stage of disease. The model supports current diagnostic sampling approaches and control measures for the removal and destruction of nervous system tissues in slaughtered cattle.

  13. 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. © 2014 John Wiley & Sons Ltd/CNRS.

  14. Spongiform neurodegenerative disease in a Persian kitten.

    PubMed

    Salvadori, Claudia; Lossi, Laura; Arispici, Mario; Cantile, Carlo

    2007-06-01

    A congenital encephalopathy with spongiform degeneration and prominent neuronal apoptosis was observed in a 4-month-old Persian male cat with a history of depressed mental status and ataxia. On clinical examination, signs included right head tilt, ventroflexion of the head and neck, and tetraparesis. Histological examination of the central nervous system revealed multifocal, bilateral and symmetrical vacuolar degeneration of the neuropil, mainly involving the cerebellar and vestibular nuclei area, the caudal colliculi, the mesencephalic nuclei, the tegmental area and the deeper layer of the cerebral cortex. Accumulation of phosphorylated neurofilaments was detected in neuronal perikarya of the deep cortical layers, hippocampus and thalamus. Numerous pyknotic and apoptotic neurons were also observed in the cerebral cortex. These neuropathological changes differ from those observed in previous reports of spongiform degeneration of the grey matter in cats and were suggestive of a congenital neurodegenerative disease.

  15. Detection of bovine spongiform encephalopathy-specific PrP(Sc) by treatment with heat and guanidine thiocyanate.

    PubMed

    Meyer, R K; Oesch, B; Fatzer, R; Zurbriggen, A; Vandevelde, M

    1999-11-01

    The conversion of a ubiquitous cellular protein (PrP(C)), an isoform of the prion protein (PrP), to the pathology-associated isoform PrP(Sc) is one of the hallmarks of transmissible spongiform encephalopathies such as bovine spongiform encephalopathy (BSE). Accumulation of PrP(Sc) has been used to diagnose BSE. Here we describe a quantitative enzyme-linked immunosorbent assay (ELISA) that involves antibodies against epitopes within the protease-resistant core of the PrP molecule to measure the amount of PrP in brain tissues from animals with BSE and normal controls. In native tissue preparations, little difference was found between the two groups. However, following treatment of the tissue with heat and guanidine thiocyanate (Gh treatment), the ELISA discriminated BSE-specific PrP(Sc) from PrP(C) in bovine brain homogenates. PrP(Sc) was identified by Western blot, centrifugation, and protease digestion experiments. It was thought that folding or complexing of PrP(Sc) is most probably reversed by the Gh treatment, making hidden antigenic sites accessible. The digestion experiments also showed that protease-resistant PrP in BSE is more difficult to detect than that in hamster scrapie. While the concentration of PrP(C) in cattle is similar to that in hamsters, PrP(Sc) sparse in comparison. The detection of PrP(Sc) by a simple physicochemical treatment without the need for protease digestion, as described in this study, could be applied to develop a diagnostic assay to screen large numbers of samples.

  16. 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

  17. 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.

  18. Transcriptional changes in the brains of cattle orally infected with the bovine spongiform encephalopathy agent precede detection of infectivity.

    PubMed

    Tang, Yue; Xiang, Wei; Hawkins, Steve A C; Kretzschmar, Hans A; Windl, Otto

    2009-09-01

    Bovine spongiform encephalopathy (BSE) is a fatal, transmissible, neurodegenerative disease of cattle. BSE can be transmitted experimentally between cattle through the oral route, and in this study, brain tissue samples from animals at different time points postinoculation were analyzed for changes in gene expression. The aims of this study were to identify differentially regulated genes during the progression of BSE using microarray-based gene expression profiling and to understand the effect of prion pathogenesis on gene expression. A total of 114 genes were found to be differentially regulated over the time course of the infection, and many of these 114 genes encode proteins involved in immune response, apoptosis, cell adhesion, stress response, and transcription. This study also revealed a broad correlation between gene expression profiles and the progression of BSE in cattle. At 21 months postinoculation, the largest number of differentially regulated genes was detected, suggesting that there are many pathogenic processes in the animal brain even prior to the detection of infectivity in the central nervous systems of these orally infected cattle. Moreover, evidence is presented to suggest that it is possible to predict the infectious status of animals using the expression profiles from this study.

  19. Direct costs of bovine spongiform encephalopathy control measures in Germany.

    PubMed

    Probst, C; Gethmann, J M; Heuser, R; Niemann, H; Conraths, F J

    2013-12-01

    On 26 November 2000, the first autochthonous case of bovine spongiform encephalopathy (BSE) was detected in Germany. Since then, a total of 413 BSE cases have been confirmed, resulting in the culling and destruction of 17 313 heads of cattle. In view of the possible risks for human and animal health, Germany has adopted EU regulations along with some additional requirements concerning active surveillance and response measures after detecting a BSE-positive animal. In this study, we used a stochastic model to estimate the costs incurred by the ensuing legislative amendments responding to BSE between November 2000 and December 2010. The total costs were estimated to range between 1847 and 2094 million Euros. They peaked in 2001 (about 394 million Euros) and declined since. About 54% of the costs (approximately 1000 million Euros) were incurred by the extension of the feed ban for animal protein to all farmed livestock. Active surveillance accounted for 21% (405 million Euros), the incineration of animal protein for 13% (249 million Euros) and the removal of specified risk material for 11% (225 million Euros). Only 1% of the costs was related to response measures after detecting a BSE-positive animal, including indemnity payments for culled cattle and confiscated carcasses at the slaughterhouse. © 2013 Blackwell Verlag GmbH.

  20. 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

  1. 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.

  2. Risks of transmitting ruminant spongiform encephalopathies (prion diseases) by semen and embryo transfer techniques.

    PubMed

    Wrathall, A E; Holyoak, G R; Parsonson, I M; Simmons, H A

    2008-09-15

    Early experiments suggested that scrapie transmission via sheep embryos was a possibility, and gave rise to much controversy. However, when account is taken of the complex genetic effects on ovine susceptibility to scrapie, and of the several different scrapie strains with different clinical and pathological effects, the overall conclusion now is that transmission of classical scrapie by embryo transfer is very unlikely if appropriate precautions are taken. Recent embryo transfer studies have confirmed this. Other studies in sheep have shown that from about the middle of pregnancy the placental trophoblast is liable to scrapie infection in genetically susceptible ewes if the fetus is also susceptible. Since the contrary is also true, use of resistant ewes as embryo recipients could add to the safety of the embryo transfer, at least for classical scrapie. There has been little recent research on scrapie transmission via semen in sheep, and, with hindsight, the early studies, though negative, were inadequate. There is scant information on scrapie transfer via goat semen or embryos, although one study did find that bovine spongiform encephalopathy (BSE) was not transmitted via goat embryos. In cattle it has been shown that, if appropriate precautions are taken, the risks of transmitting BSE via semen and in vivo-derived embryos are negligible, and this conclusion has gained worldwide acceptance. Research on TSE transmission via reproductive technologies in deer has not yet been done, but information on the pathogenesis and epidemiology of chronic wasting disease (CWD) of deer, and on transmission risks in other species, provides optimism that transmission of CWD via semen and embryos of deer is unlikely. The presence of TSE infectivity in blood and various other tissues of infected animals, particularly sheep, gives rise to concerns that certain biological products currently used in reproductive technologies, e.g. pituitary gonadotrophins for superovulation, and

  3. Evaluation of a Closed Loop Inductive Power Transmission System on an Awake Behaving Animal Subject

    PubMed Central

    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

  4. 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.

  5. Early animal farming and zoonotic disease dynamics: modelling brucellosis transmission in Neolithic goat populations.

    PubMed

    Fournié, Guillaume; Pfeiffer, Dirk U; Bendrey, Robin

    2017-02-01

    Zoonotic pathogens are frequently hypothesized as emerging with the origins of farming, but evidence of this is elusive in the archaeological records. To explore the potential impact of animal domestication on zoonotic disease dynamics and human infection risk, we developed a model simulating the transmission of Brucella melitensis within early domestic goat populations. The model was informed by archaeological data describing goat populations in Neolithic settlements in the Fertile Crescent, and used to assess the potential of these populations to sustain the circulation of Brucella. Results show that the pathogen could have been sustained even at low levels of transmission within these domestic goat populations. This resulted from the creation of dense populations and major changes in demographic characteristics. The selective harvesting of young male goats, likely aimed at improving the efficiency of food production, modified the age and sex structure of these populations, increasing the transmission potential of the pathogen within these populations. Probable interactions between Neolithic settlements would have further promoted pathogen maintenance. By fostering conditions suitable for allowing domestic goats to become reservoirs of Brucella melitensis, the early stages of agricultural development were likely to promote the exposure of humans to this pathogen.

  6. Early animal farming and zoonotic disease dynamics: modelling brucellosis transmission in Neolithic goat populations

    PubMed Central

    Pfeiffer, Dirk U.; Bendrey, Robin

    2017-01-01

    Zoonotic pathogens are frequently hypothesized as emerging with the origins of farming, but evidence of this is elusive in the archaeological records. To explore the potential impact of animal domestication on zoonotic disease dynamics and human infection risk, we developed a model simulating the transmission of Brucella melitensis within early domestic goat populations. The model was informed by archaeological data describing goat populations in Neolithic settlements in the Fertile Crescent, and used to assess the potential of these populations to sustain the circulation of Brucella. Results show that the pathogen could have been sustained even at low levels of transmission within these domestic goat populations. This resulted from the creation of dense populations and major changes in demographic characteristics. The selective harvesting of young male goats, likely aimed at improving the efficiency of food production, modified the age and sex structure of these populations, increasing the transmission potential of the pathogen within these populations. Probable interactions between Neolithic settlements would have further promoted pathogen maintenance. By fostering conditions suitable for allowing domestic goats to become reservoirs of Brucella melitensis, the early stages of agricultural development were likely to promote the exposure of humans to this pathogen. PMID:28386446

  7. 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.

  8. Evidence of subclinical prion disease in aged mice following exposure to bovine spongiform encephalopathy.

    PubMed

    Brown, Karen L; Mabbott, Neil A

    2014-01-01

    The occurrence of variant Creutzfeldt-Jakob (vCJD) disease in humans was almost certainly the result of consumption of food contaminated with bovine spongiform encephalopathy (BSE) prions. Despite probable widespread exposure of the UK population to BSE-contaminated food in the 1980s, vCJD has been identified predominantly in young individuals, and there have been fewer cases of clinical disease than anticipated. The reasons for this are uncertain. Following peripheral exposure, many prions replicate within the lymphoid tissues before infecting the central nervous system. We have shown that the effects of host age on the microarchitecture of the spleen significantly impair susceptibility to mouse-adapted prions after peripheral exposure. The transmission of prions between different mammalian species is considered to be limited by the 'species barrier', which is dependent on several factors, including an intact immune system. Thus, cross-species prion transmission may be much less efficient in aged individuals. To test this hypothesis, we compared prion pathogenesis in groups of young (6-8 weeks old) and aged (600 days old) mice injected with primary BSE brain homogenate. We showed that prion pathogenesis was impaired dramatically in aged mice when compared with young animals. Whereas most young mice succumbed to clinical prion disease, all aged mice failed to develop clinical disease during their lifespans. However, the demonstration that prion accumulation was detected in the lymphoid tissues of some aged mice after injection with primary BSE brain homogenate, in the absence of clinical signs of prion disease, has important implications for human health.

  9. Zooprophylaxis or zoopotentiation: the outcome of introducing animals on vector transmission is highly dependent on the mosquito mortality while searching

    PubMed Central

    Saul, Allan

    2003-01-01

    Background Zooprophylaxis, the diversion of disease carrying insects from humans to animals, may reduce transmission of diseases such as malaria. However, as the number of animals increases, improved availability of blood meals may increase mosquito survival, thereby countering the impact of diverting feeds. Methods Computer simulation was used to examine the effects of animals on the transmission of human diseases by mosquitoes. Three scenarios were modelled: (1) endemic transmission, where the animals cannot be infected, eg. malaria; (2) epidemic transmission, where the animals cannot be infected but humans remain susceptible, e.g. malaria; (3) epidemic disease, where both humans and animals can be infected, but develop sterile immunity, eg. Japanese encephalitis B. For each, the passive impact of animals as well as the use of animals as bait to attract mosquitoes to insecticide was examined. The computer programmes are available from the author. A teaching model accompanies this article. Results For endemic and epidemic malaria with significant searching-associated vector mortality, changing animal numbers and accessibility had little impact. Changing the accessibility of the humans had a much greater effect. For diseases with an animal amplification cycle, the most critical factor was the proximity of the animals to the mosquito breeding sites. Conclusion Estimates of searching-associated vector mortality are essential before the effects of changing animal husbandry practices can be predicted. With realistic values of searching-associated vector mortality rates, zooprophylaxis may be ineffective. However, use of animals as bait to attract mosquitoes to insecticide is predicted to be a promising strategy. PMID:14565850

  10. 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

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

    PubMed

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

    2016-02-01

    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. 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). 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. 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.

  12. Genotype-dependent molecular evolution of sheep bovine spongiform encephalopathy (BSE) prions in vitro affects their zoonotic potential.

    PubMed

    Krejciova, Zuzana; Barria, Marcelo A; Jones, Michael; Ironside, James W; Jeffrey, Martin; González, Lorenzo; Head, Mark W

    2014-09-19

    Prion diseases are rare fatal neurological conditions of humans and animals, one of which (variant Creutzfeldt-Jakob disease) is known to be a zoonotic form of the cattle disease bovine spongiform encephalopathy (BSE). What makes one animal prion disease zoonotic and others not is poorly understood, but it appears to involve compatibility between the prion strain and the host prion protein sequence. Concerns have been raised that the United Kingdom sheep flock may have been exposed to BSE early in the cattle BSE epidemic and that serial BSE transmission in sheep might have resulted in adaptation of the agent, which may have come to phenotypically resemble scrapie while maintaining its pathogenicity for humans. We have modeled this scenario in vitro. Extrapolation from our results suggests that if BSE were to infect sheep in the field it may, with time and in some sheep genotypes, become scrapie-like at the molecular level. However, the results also suggest that if BSE in sheep were to come to resemble scrapie it would lose its ability to affect humans. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Genotype-dependent Molecular Evolution of Sheep Bovine Spongiform Encephalopathy (BSE) Prions in Vitro Affects Their Zoonotic Potential*

    PubMed Central

    Krejciova, Zuzana; Barria, Marcelo A.; Jones, Michael; Ironside, James W.; Jeffrey, Martin; González, Lorenzo; Head, Mark W.

    2014-01-01

    Prion diseases are rare fatal neurological conditions of humans and animals, one of which (variant Creutzfeldt-Jakob disease) is known to be a zoonotic form of the cattle disease bovine spongiform encephalopathy (BSE). What makes one animal prion disease zoonotic and others not is poorly understood, but it appears to involve compatibility between the prion strain and the host prion protein sequence. Concerns have been raised that the United Kingdom sheep flock may have been exposed to BSE early in the cattle BSE epidemic and that serial BSE transmission in sheep might have resulted in adaptation of the agent, which may have come to phenotypically resemble scrapie while maintaining its pathogenicity for humans. We have modeled this scenario in vitro. Extrapolation from our results suggests that if BSE were to infect sheep in the field it may, with time and in some sheep genotypes, become scrapie-like at the molecular level. However, the results also suggest that if BSE in sheep were to come to resemble scrapie it would lose its ability to affect humans. PMID:25100723

  14. [Biology of non-conventional transmissible agents or prions].

    PubMed

    Dormont, D

    1998-02-01

    Transmissible subacute spongiform encephalopathies (TSE) are a group of human and animal diseases which includes Creutzfeldt-Jakob disease, Gerstmann-Straüssler-Scheinker syndrome (GSS), Kuru, fatal familial insomnia (FFI), scrapie in sheep and goat, mink and feline transmissible encephalopathy, chronic wasting disease, and bovine spongiforme encephalopathy (BSE). TSE are transmissible among individuals of the same species and some of different species. These diseases stem from a specific category of agents that have biological and physiochemical characteristics unlike other micro-organisms; they are known as transmissible spongiform encephalopathy agent (TSA), prions, or virinos. So far, despite considerable progress made in the molecular biology toward the understanding of neurological injury, the nature of the TSA/prions remains unknown. TSE are characterised by the pathognomic accumulation, within the central nervous system of the infected individual, of a normal protein from the host organism, the PrP (prion protein). Differences between the PrP isolated from normal individuals (PrP-c) and PrP isolated from infected individuals (PrP-res) have been investigated. There are no differences in the sequence in amino acids, and the secondary structure seems identical, but since normal PrP is totally degraded by proteinase K pathological PrP resists to enzymatic digestion. One can therefore describe two PrP isoforms: a normal isoform, the PrP-c (c for cellular), sensitive to proteinase K and present in the normal individual and in the infected patients or animals: and a pathological isoform, the PrP-res, resistant to proteinase K and present in amount proportional to the infectivity in the brains of infected individuals. The presence of TSA/prions is detectable in the spleens of infected animals early after inoculation; it is then present in the CNS following a period not exceeding a half of the total length of the experimental disease. In the CNS, PrP-res is the

  15. 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

    2015-06-30

    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.

  16. 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

  17. Shell disorder, immune evasion and transmission behaviors among human and animal retroviruses.

    PubMed

    Goh, Gerard Kian-Meng; Dunker, A Keith; Uversky, Vladimir N

    2015-08-01

    This study involves measurements of percentages of intrinsic disorder (PIDs) in the GAG protein shells of various retroviruses. Unique patterns of shell protein disorder can be seen especially when GAG proteins (matrix M, capsid C, and nucleocapsid N) of primate and non-primate retroviruses are compared. HIV-1 presents the most unique pattern of disorder distribution with generally high levels of disorder in all three proteins, while EIAV (PIDs:: 26, 29, 13) is diametrically different from HIV-1 (N C M PIDs: 39.5 ± 3.0, 44.5 ± 2.6, 56.5 ± 10.8). The HTLV viruses (CPID: 32.8 ± 3.4) resemble HIV-2 (C PID: 26.6 ± 2.9) with a moderately disordered capsid. Totally distinct patterns, however, are seen for the non-primate retroviruses. They generally have highly disordered nucleocapsids (PID > 65%) and more ordered outer shells especially the matrix. These characteristics might be attributed to the differences in the way the retroviruses are transmitted, with non-primate viruses having greater non-sexual transmission components such as oral-fecal transmission. These differences are also evolutionarily related to the ways the viruses evade the host immune systems, and thus, have implications for oncolytic virotherapy and animal models in vaccine research. The importance of protein shell disorder in immune evasion, as related to the case of HIV-1, and the difficult search for its vaccines are highlighted.

  18. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Chronic Wasting Disease and Potential Transmission to Humans

    PubMed Central

    Maddox, Ryan A.; Williams, Elizabeth S.; Miller, Michael W.; Gambetti, Pierluigi; Schonberger, Lawrence B.

    2004-01-01

    Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts of the United States. Although detection in some areas may be related to increased surveillance, introduction of CWD due to translocation or natural migration of animals may account for some new foci of infection. Increasing spread of CWD has raised concerns about the potential for increasing human exposure to the CWD agent. The foodborne transmission of bovine spongiform encephalopathy to humans indicates that the species barrier may not completely protect humans from animal prion diseases. Conversion of human prion protein by CWD-associated prions has been demonstrated in an in vitro cell-free experiment, but limited investigations have not identified strong evidence for CWD transmission to humans. More epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions. PMID:15207045

  20. Presence of subclinical infection in gene-targeted human prion protein transgenic mice exposed to atypical bovine spongiform encephalopathy.

    PubMed

    Wilson, Rona; Dobie, Karen; Hunter, Nora; Casalone, Cristina; Baron, Thierry; Barron, Rona M

    2013-12-01

    The transmission of bovine spongiform encephalopathy (BSE) to humans, leading to variant Creutzfeldt-Jakob disease has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health. Until recently, TSE disease in cattle was thought to be caused by a single agent strain, BSE, also known as classical BSE, or BSE-C. However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. To model the risk to human health, we previously inoculated these two forms of atypical BSE (BASE and BSE-H) into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP) (HuTg) but were unable to detect any signs of TSE pathology in these mice. However, despite the absence of TSE pathology, upon subpassage of some BASE-challenged HuTg mice, a TSE was observed in recipient gene-targeted bovine PrP Tg (Bov6) mice but not in HuTg mice. Disease transmission from apparently healthy individuals indicates the presence of subclinical BASE infection in mice expressing human PrP that cannot be identified by current diagnostic methods. However, due to the lack of transmission to HuTg mice on subpassage, the efficiency of mouse-to-mouse transmission of BASE appears to be low when mice express human rather than bovine PrP.

  1. Squirrel monkeys (Saimiri sciureus) infected with the agent of bovine spongiform encephalopathy develop tau pathology.

    PubMed

    Piccardo, P; Cervenak, J; Yakovleva, O; Gregori, L; Pomeroy, K; Cook, A; Muhammad, F S; Seuberlich, T; Cervenakova, L; Asher, D M

    2012-07-01

    Squirrel monkeys (Saimiri sciureus) were infected experimentally with the agent of classical bovine spongiform encephalopathy (BSE). Two to four years later, six of the monkeys developed alterations in interactive behaviour and cognition and other neurological signs typical of transmissible spongiform encephalopathy (TSE). At necropsy examination, the brains from all of the monkeys showed pathological changes similar to those described in variant Creutzfeldt-Jakob disease (vCJD) of man, except that the squirrel monkey brains contained no PrP-amyloid plaques typical of that disease. Constant neuropathological features included spongiform degeneration, gliosis, deposition of abnormal prion protein (PrP(TSE)) and many deposits of abnormally phosphorylated tau protein (p-Tau) in several areas of the cerebrum and cerebellum. Western blots showed large amounts of proteinase K-resistant prion protein in the central nervous system. The striking absence of PrP plaques (prominent in brains of cynomolgus macaques [Macaca fascicularis] with experimentally-induced BSE and vCJD and in human patients with vCJD) reinforces the conclusion that the host plays a major role in determining the neuropathology of TSEs. Results of this study suggest that p-Tau, found in the brains of all BSE-infected monkeys, might play a role in the pathogenesis of TSEs. Whether p-Tau contributes to development of disease or appears as a secondary change late in the course of illness remains to be determined. Published by Elsevier Ltd.

  2. A mathematical framework for estimating pathogen transmission fitness and inoculum size using data from a competitive mixtures animal model.

    PubMed

    McCaw, James M; Arinaminpathy, Nimalan; Hurt, Aeron C; McVernon, Jodie; McLean, Angela R

    2011-04-01

    We present a method to measure the relative transmissibility ("transmission fitness") of one strain of a pathogen compared to another. The model is applied to data from "competitive mixtures" experiments in which animals are co-infected with a mixture of two strains. We observe the mixture in each animal over time and over multiple generations of transmission. We use data from influenza experiments in ferrets to demonstrate the approach. Assessment of the relative transmissibility between two strains of influenza is important in at least three contexts: 1) Within the human population antigenically novel strains of influenza arise and compete for susceptible hosts. 2) During a pandemic event, a novel sub-type of influenza competes with the existing seasonal strain(s). The unfolding epidemiological dynamics are dependent upon both the population's susceptibility profile and the inherent transmissibility of the novel strain compared to the existing strain(s). 3) Neuraminidase inhibitors (NAIs), while providing significant potential to reduce transmission of influenza, exert selective pressure on the virus and so promote the emergence of drug-resistant strains. Any adverse outcome due to selection and subsequent spread of an NAI-resistant strain is exquisitely dependent upon the transmission fitness of that strain. Measurement of the transmission fitness of two competing strains of influenza is thus of critical importance in determining the likely time-course and epidemiology of an influenza outbreak, or the potential impact of an intervention measure such as NAI distribution. The mathematical framework introduced here also provides an estimate for the size of the transmitted inoculum. We demonstrate the framework's behaviour using data from ferret transmission studies, and through simulation suggest how to optimise experimental design for assessment of transmissibility. The method introduced here for assessment of mixed transmission events has applicability beyond

  3. Carriage of methicillin-resistant Staphylococcus pseudintermedius in small animal veterinarians: indirect evidence of zoonotic transmission.

    PubMed

    Paul, N C; Moodley, A; Ghibaudo, G; Guardabassi, L

    2011-12-01

    and proper preventative measures should be taken to avoid MRSP transmission from animal patients.

  4. Detection and Control of Prion Diseases in Food Animals

    PubMed Central

    Hedlin, Peter; Taschuk, Ryan; Potter, Andrew; Griebel, Philip; Napper, Scott

    2012-01-01

    Transmissible spongiform encephalopathies (TSEs), or prion diseases, represent a unique form of infectious disease based on misfolding of a self-protein (PrPC) into a pathological, infectious conformation (PrPSc). Prion diseases of food animals gained notoriety during the bovine spongiform encephalopathy (BSE) outbreak of the 1980s. In particular, disease transmission to humans, to the generation of a fatal, untreatable disease, elevated the perspective on livestock prion diseases from food production to food safety. While the immediate threat posed by BSE has been successfully addressed through surveillance and improved management practices, another prion disease is rapidly spreading. Chronic wasting disease (CWD), a prion disease of cervids, has been confirmed in wild and captive populations with devastating impact on the farmed cervid industries. Furthermore, the unabated spread of this disease through wild populations threatens a natural resource that is a source of considerable economic benefit and national pride. In a worst-case scenario, CWD may represent a zoonotic threat either through direct transmission via consumption of infected cervids or through a secondary food animal, such as cattle. This has energized efforts to understand prion diseases as well as to develop tools for disease detection, prevention, and management. Progress in each of these areas is discussed. PMID:23738120

  5. Retinal Fluorescence Spectroscopy for Diagnosis of Transmissible Spongiform Encephalopathies

    USDA-ARS?s Scientific Manuscript database

    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...

  6. Phenotype shift from atypical scrapie to CH1641 following experimental transmission in sheep.

    PubMed

    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.

  7. Experimental inoculation of raccoons (Procyon lotor) with Spiroplasma mirum and transmissible mink encephalopathy (TME).

    PubMed

    Hamir, Amir N; Greenlee, Justin J; Stanton, Thad B; Smith, Jodi D; Doucette, Stephanie; Kunkle, Robert A; Stasko, Judith A; Richt, Juergen A; Kehrli, Marcus E

    2011-01-01

    The primary objective of this study was to determine whether or not Spiroplasma mirum would be capable of producing lesions of transmissible spongiform encephalopathy (TSE) when inoculated in raccoons (Procyon lotor) and, if that was possible, to compare the clinicopathological findings with those of transmissible mink encephalopathy (TME) in the same experimental model. For this purpose, 5 groups (n = 5) of raccoon kits were inoculated intracerebrally with either S. mirum and/or TME. Two other groups (n = 5) of raccoon kits served as sham-inoculated controls. All animals inoculated with TME, either alone or in combination, showed clinical signs of neurologic disorder and were euthanized within 6 mo post-inoculation (MPI). None of the carcasses revealed gross lesions. Spongiform encephalopathy was observed by light microscopy and the presence of abnormal disease-causing prion protein (PrP(d)) was detected by immunohistochemistry (IHC) and Western blot (WB) techniques in only the raccoons administered TME. Raccoons inoculated with Spiroplasma, but not administered TME agent, were euthanized at 30 MPI. They did not show clinical neurologic signs, their brains did not have lesions of spongiform encephalopathy, and their tissues were negative for S. mirum by polymerase chain reaction (PCR) and for PrP(d) by IHC and WB techniques. The results of this study indicate that Spiroplasma mirum does not induce TSE-like disease in raccoons.

  8. Experimental inoculation of raccoons (Procyon lotor) with Spiroplasma mirum and transmissible mink encephalopathy (TME)

    PubMed Central

    Hamir, Amir N.; Greenlee, Justin J.; Stanton, Thad B.; Smith, Jodi D.; Doucette, Stephanie; Kunkle, Robert A.; Stasko, Judith A.; Richt, Juergen A.; Kehrli, Marcus E.

    2011-01-01

    The primary objective of this study was to determine whether or not Spiroplasma mirum would be capable of producing lesions of transmissible spongiform encephalopathy (TSE) when inoculated in raccoons (Procyon lotor) and, if that was possible, to compare the clinicopathological findings with those of transmissible mink encephalopathy (TME) in the same experimental model. For this purpose, 5 groups (n = 5) of raccoon kits were inoculated intracerebrally with either S. mirum and/or TME. Two other groups (n = 5) of raccoon kits served as sham-inoculated controls. All animals inoculated with TME, either alone or in combination, showed clinical signs of neurologic disorder and were euthanized within 6 mo post-inoculation (MPI). None of the carcasses revealed gross lesions. Spongiform encephalopathy was observed by light microscopy and the presence of abnormal disease-causing prion protein (PrPd) was detected by immunohistochemistry (IHC) and Western blot (WB) techniques in only the raccoons administered TME. Raccoons inoculated with Spiroplasma, but not administered TME agent, were euthanized at 30 MPI. They did not show clinical neurologic signs, their brains did not have lesions of spongiform encephalopathy, and their tissues were negative for S. mirum by polymerase chain reaction (PCR) and for PrPd by IHC and WB techniques. The results of this study indicate that Spiroplasma mirum does not induce TSE-like disease in raccoons. PMID:21461191

  9. Disrupted Glutamatergic Transmission in Prefrontal Cortex Contributes to Behavioral Abnormality in an Animal Model of ADHD.

    PubMed

    Cheng, Jia; Liu, Aiyi; Shi, Michael Y; Yan, Zhen

    2017-02-08

    Spontaneously hypertensive rats (SHR) are the most widely used animal model for the study of attention deficit hyperactivity disorder (ADHD). Here we sought to reveal the neuronal circuits and molecular basis of ADHD and its potential treatment using SHR. Combined electrophysiological, biochemical, pharmacological, chemicogenetic and behavioral approaches were utilized. We found that AMPAR-mediated synaptic transmission in pyramidal neurons of prefrontal cortex (PFC) was diminished in SHR, which was correlated with the decreased surface expression of AMPAR subunits. Administration of methylphenidate (a psychostimulant drug used to treat ADHD), which blocks dopamine transporters and norepinephrine transporters, ameliorated the behavioral deficits of adolescent SHR and restored AMPAR-mediated synaptic function. Activation of PFC pyramidal neurons with a CaMKII-driven Gq-coupled DREADD (designer receptor exclusively activated by designer drug) also led to the elevation of AMPAR function and the normalization of ADHD-like behaviors in SHR. These results suggest that the disrupted function of AMPARs in PFC may underlie the behavioral deficits in adolescent SHR and enhancing PFC activity could be a treatment strategy for ADHD.Neuropsychopharmacology accepted article preview online, 08 February 2017. doi:10.1038/npp.2017.30.

  10. Climate variability, animal reservoir and transmission of scrub typhus in Southern China.

    PubMed

    Wei, Yuehong; Huang, Yong; Li, Xiaoning; Ma, Yu; Tao, Xia; Wu, Xinwei; Yang, Zhicong

    2017-03-01

    We aimed to evaluate the relationships between climate variability, animal reservoirs and scrub typhus incidence in Southern China. We obtained data on scrub typhus cases in Guangzhou every month from 2006 to 2014 from the Chinese communicable disease network. Time-series Poisson regression models and distributed lag nonlinear models (DLNM) were used to evaluate the relationship between risk factors and scrub typhus. Wavelet analysis found the incidence of scrub typhus cycled with a period of approximately 8-12 months and long-term trends with a period of approximately 24-36 months. The DLNM model shows that relative humidity, rainfall, DTR, MEI and rodent density were associated with the incidence of scrub typhus. Our findings suggest that the incidence scrub typhus has two main temporal cycles. Determining the reason for this trend and how it can be used for disease control and prevention requires additional research. The transmission of scrub typhus is highly dependent on climate factors and rodent density, both of which should be considered in prevention and control strategies for scrub typhus.

  11. Climate variability, animal reservoir and transmission of scrub typhus in Southern China

    PubMed Central

    Li, Xiaoning; Ma, Yu; Tao, Xia; Wu, Xinwei

    2017-01-01

    Objectives We aimed to evaluate the relationships between climate variability, animal reservoirs and scrub typhus incidence in Southern China. Methods We obtained data on scrub typhus cases in Guangzhou every month from 2006 to 2014 from the Chinese communicable disease network. Time-series Poisson regression models and distributed lag nonlinear models (DLNM) were used to evaluate the relationship between risk factors and scrub typhus. Results Wavelet analysis found the incidence of scrub typhus cycled with a period of approximately 8–12 months and long-term trends with a period of approximately 24–36 months. The DLNM model shows that relative humidity, rainfall, DTR, MEI and rodent density were associated with the incidence of scrub typhus. Conclusions Our findings suggest that the incidence scrub typhus has two main temporal cycles. Determining the reason for this trend and how it can be used for disease control and prevention requires additional research. The transmission of scrub typhus is highly dependent on climate factors and rodent density, both of which should be considered in prevention and control strategies for scrub typhus. PMID:28273079

  12. 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.

  13. 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

  14. Assessing the susceptibility of transgenic mice overexpressing deer prion protein to bovine spongiform encephalopathy.

    PubMed

    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; Spiropoulos, John

    2014-02-01

    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.

  15. Increased susceptibility of transgenic mice expressing human PrP to experimental sheep bovine spongiform encephalopathy is not due to increased agent titre in sheep brain tissue

    PubMed Central

    Plinston, Chris; Hart, Patricia; Hunter, Nora; Manson, Jean C.

    2014-01-01

    Bovine spongiform encephalopathy (BSE) in cattle and variant Creutzfeldt–Jakob disease in humans have previously been shown to be caused by the same strain of transmissible spongiform encephalopathy agent. It is hypothesized that the agent spread to humans following consumption of food products prepared from infected cattle. Despite evidence supporting zoonotic transmission, mouse models expressing human prion protein (HuTg) have consistently shown poor transmission rates when inoculated with cattle BSE. Higher rates of transmission have however been observed when these mice are exposed to BSE that has been experimentally transmitted through sheep or goats, indicating that humans may potentially be more susceptible to BSE from small ruminants. Here we demonstrate that increased transmissibility of small ruminant BSE to HuTg mice was not due to replication of higher levels of infectivity in sheep brain tissue, and is instead due to other specific changes in the infectious agent. PMID:24828334

  16. Increased susceptibility of transgenic mice expressing human PrP to experimental sheep bovine spongiform encephalopathy is not due to increased agent titre in sheep brain tissue.

    PubMed

    Plinston, Chris; Hart, Patricia; Hunter, Nora; Manson, Jean C; Barron, Rona M

    2014-08-01

    Bovine spongiform encephalopathy (BSE) in cattle and variant Creutzfeldt-Jakob disease in humans have previously been shown to be caused by the same strain of transmissible spongiform encephalopathy agent. It is hypothesized that the agent spread to humans following consumption of food products prepared from infected cattle. Despite evidence supporting zoonotic transmission, mouse models expressing human prion protein (HuTg) have consistently shown poor transmission rates when inoculated with cattle BSE. Higher rates of transmission have however been observed when these mice are exposed to BSE that has been experimentally transmitted through sheep or goats, indicating that humans may potentially be more susceptible to BSE from small ruminants. Here we demonstrate that increased transmissibility of small ruminant BSE to HuTg mice was not due to replication of higher levels of infectivity in sheep brain tissue, and is instead due to other specific changes in the infectious agent. © 2014 The Authors.

  17. Reverse zoonotic disease transmission (zooanthroponosis): a systematic review of seldom-documented human biological threats to animals.

    PubMed

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

    2014-01-01

    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. 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. 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. 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.

  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. Transmission of Schistosoma japonicum by humans and domestic animals in the Yangtze River valley, Anhui province, China.

    PubMed

    Wang, Tian-Ping; Vang Johansen, Maria; Zhang, Shi-Qing; Wang, Feng-Feng; Wu, Wei-Duo; Zhang, Gong-Hua; Pan, Xin-Ping; Ju, Yang; Ørnbjerg, Niels

    2005-01-01

    The aim of the present work was to assess the relative contribution to transmission of Schistosoma japonicum by humans and domestic animals in two villages in the Yangtze River valley in Anhui province, China. A cross-sectional survey was conducted to determine the prevalence and intensity of S. japonicum in humans, cattle, water buffaloes, horses, pigs, goats, dogs and cats. Additionally, for each host species the number of individuals and the mean faecal excretion per day was determined. Results showed that both prevalence and intensity of infection varied significantly between species and between the two villages and neither of the variables gave an adequate picture of the potential transmission. Total daily egg excretion was significantly higher in Chenqiao village compared with Guanghui village. Whereas humans were the main contributors to transmission of schistosomiasis in Guanghui village (80.4%), water buffaloes accounted for nearly 90% and goats for more than 5% of the transmission in Chenqiao village. Hence, the present study suggests that schistosomiasis transmission might vary significantly within Chinese farm districts and successful control should rely on prior transmission index determinations on major potential contributors rather than routine data of prevalence and intensity of infection. Further studies should determine the value of adding other transmission variables like egg hatchability and faecal deposition habits.

  20. Calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models.

    PubMed

    Uchitel, Osvaldo D; González Inchauspe, Carlota; Di Guilmi, Mariano N

    2014-03-01

    One of the outstanding developments in clinical neurology has been the identification of ion channel mutations as the origin of a wide variety of inherited disorders like migraine, epilepsy, and ataxia. The study of several channelopathies has provided crucial insights into the molecular mechanisms, pathogenesis, and therapeutic approaches to complex neurological diseases. This review addresses the mutations underlying familial hemiplegic migraine (FHM) with particular interest in Cav2.1 (i.e., P/Q-type) voltage-activated Ca(2+) channel FHM type-1 mutations (FHM1). Transgenic mice harboring the human pathogenic FHM1 mutation R192Q or S218L (KI) have been used as models to study neurotransmission at several central and peripheral synapses. FHM1 KI mice are a powerful tool to explore presynaptic regulation associated with expression of Cav2.1 channels. FHM1 Cav2.1 channels activate at more hyperpolarizing potentials and show an increased open probability. These biophysical alterations may lead to a gain-of-function on synaptic transmission depending upon factors such as action potential waveform and/or Cav2.1 splice variants and auxiliary subunits. Analysis of FHM knock-in mouse models has demonstrated a deficient regulation of the cortical excitation/inhibition (E/I) balance. The resulting excessive increases in cortical excitation may be the mechanisms that underlie abnormal sensory processing together with an increase in the susceptibility to cortical spreading depression (CSD). Increasing evidence from FHM KI animal studies support the idea that CSD, the underlying mechanism of aura, can activate trigeminal nociception, and thus trigger the headache mechanisms.

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

    PubMed

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

    2015-05-26

    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. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

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

    PubMed Central

    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.

    2015-01-01

    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

  3. Abnormal prion protein is associated with changes of plasma membranes and endocytosis in bovine spongiform encephalopathy (BSE)-affected cattle brains.

    PubMed

    Ersdal, C; Goodsir, C M; Simmons, M M; McGovern, G; Jeffrey, M

    2009-06-01

    Transmissible spongiform encephalopathies (TSEs) or prion diseases are fatal neurodegenerative diseases of man and animals characterized by vacuolation and gliosis of neuropil and the accumulation of abnormal isoforms of a host protein known as prion protein (PrP). It is widely assumed that the abnormal isoforms of PrP (PrP(d), disease-specific form of PrP) are the proximate cause of neurodegeneration. To determine the nature of subcellular changes and their association with PrP(d) we perfusion-fixed brains of eight bovine spongiform encephalopathy (BSE)-affected cows and three control cattle for immunogold electron microscopy at two different neuroanatomical sites. All affected cattle presented plasma membrane alterations of dendrites and astrocytes that were labelled for PrP(d). PrP(d) on membranes of dendrites and occasionally of neuronal perikarya was associated with abnormal endocytotic events, including bizarre coated pits and invagination of the plasma membrane. BSE-affected cattle also presented excess and abnormal multivesicular bodies, sometimes associated to the plasma membrane perturbations. In contrast, two TSE-specific lesions, vacuolation and rare tubulovesicular bodies, were not labelled for PrP(d) as were a number of other nonspecific lesions, such as autophagy and dystrophic neurites. At least two different morphological pathways to vacuoles were recognized. When compared with other TSEs, these changes are common to those of sheep and rodent scrapie and shows that there are consistent membrane toxicity properties of PrP(d). This toxicity involves an aberration of endocytosis. However, it is by no means clear that the lesions are of sufficient severity to result in clinical deficits.

  4. 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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Nonverbal and verbal transmission of disgust from mothers to offspring: effects on children's evaluation of a novel animal.

    PubMed

    Muris, Peter; Mayer, Birgit; Borth, Maraike; Vos, Maruschka

    2013-06-01

    This study examined parent-offspring communication of disgust-related information and its effects on children's feelings of disgust and fear towards an animal. Mothers were instructed to provide information about a novel animal to their children (N=60) by studying in secrecy either disgusting or neutral attributes that were allegedly characteristic of this animal. First, mothers were instructed to do this in a nonverbal way; then they were also allowed to use verbal utterances. Results indicated that nonverbal communication of disgust by the mothers failed to produce any effects on offspring's subjective evaluations of the animal. However, verbal information transmission did have a differential impact on children's feelings of disgust and fear. That is, children to whom mothers had verbally communicated about a set of disgusting specimens not only displayed higher levels of disgust (Cohen's d=1.02) but also exhibited higher levels of fear (Cohen's d=.62) towards the novel animal as compared to children to whom mothers had verbally communicated about neutral specimens. The effect on fear was mainly due to the fact that children after the verbal neutral information exhibited a clear decline in fear, whereas children to whom mothers had provided verbal disgust information maintained a similar level of fear towards the animal. The implications of these results for the familial transmission of disgust and fear will be discussed.

  6. Prion and prion-like diseases in animals.

    PubMed

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

    2015-09-02

    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.

  7. The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission

    USDA-ARS?s Scientific Manuscript database

    Infants and children with tuberculosis (TB) account for more than 20% of cases in endemic countries. Current animal models study TB during adulthood but animal models for adolescent and infant TB are scarce. Here we propose that minipigs can be used as an animal model to study adult, adolescent and ...

  8. Bovine spongiform encephalopathy in South America: a regional preventive approach.

    PubMed

    van Gelderen, C; Gimeno, E J; Schudel, A A

    2003-04-01

    Bovine spongiform encephalopathy (BSE) is a neurodegenerative disease of cattle caused by prions that was first described in the United Kingdom (UK) in 1986. The BSE epizootic that commenced in the UK in the 1980s has since spread into other countries in Europe and Asia through exports of contaminated meat-and-bone meal or infected cattle. Over the past few years, other emerging or reemerging diseases have spread into previously free countries or regions through international trade. This negative effect of globalisation means that to implement successful preventive and strategic programmes to safeguard animal health, such programmes must, as a priority, take a regional approach. Global thinking, regional planning and local performance constitute the key factors for the successful control of animal diseases. In South America, initial preventive actions against BSE were adopted in 1989. Further measures adopted since then and based on new scientific and technical findings, have led to the demonstration that the region is free of BSE. These early preventive actions have reliably protected the region from importing BSE-infected material. An integral part of the project to determine the BSE status of South America was the training of personnel, the incorporation of technology and the provision of updated information through close relationships with international organisations and prominent international researcher workers. Regional activities aimed at harmonising BSE prevention programmes, producing objective and transparent data on the equivalence of regional BSE status and facilitating regional and international trade have recently been launched. Maintaining the BSE-free status of the region must be given high priority by the beef agro-industrial sectors.

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

    PubMed

    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

    2011-12-07

    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 ID(50). In turn, the ID(50) 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 ID(50) 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 ID(50) 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 the

  10. 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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  12. 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

  13. [Vancomycin-resistant enterococci - the nature of resistance and risk of transmission from animals to humans].

    PubMed

    Hermanovská, Lýdia; Bardoň, Jan; Čermák, Pavel

    2016-06-01

    Enterococci are part of the normal intestinal flora of humans and animals. Under certain circumstances, they are capable of extraintestinal conversion to opportunistic pathogens. They cause endogenous as well as exogenous community and nosocomial infections. The gastrointestinal tract of mammals provides them with favorable conditions for acquisition and spread of resistance genes, for example to vancomycin (van), from other symbiotic bacteria. Thus, vancomycin-resistant enterococci (VRE) become potential reservoirs and vectors of the van genes. Their occurrence in the population of the Czech Republic was first reported by Kolář et al. in 1997. Some variants of the vanA gene cluster carried on Tn1546 which encode resistance to vancomycin are identical in humans and in animals. It means that animals, especially cattle, poultry and pigs, could be an important reservoir of VRE for humans. Kolář and Bardoň detected VRE in animals in the Czech Republic for the first time in 2000. In Europe, the glycopeptide antibiotic avoparcin, used as a growth stimulator, is responsible for selection of VRE strains in animals. Strains of Enterococcus faecium from animals may offer genes of antimicrobial resistance to other enterococci or they can be directly dangerous to human. This is demonstrated by finding isolates of E. faecalis from human patients and from pigs having very similar profiles of resistance and virulence genes. The goal of the paper was to point out the similarity between isolates of human and animal strains of enterococci resistant to vancomycin, and the possibility of their bilateral transfer between humans and animals.

  14. Central nervous system extracellular matrix changes in a transgenic mouse model of bovine spongiform encephalopathy.

    PubMed

    Costa, Carme; Tortosa, Raül; Vidal, Enric; Padilla, Danielle; Torres, Juan Maria; Ferrer, Isidre; Pumarola, Martí; Bassols, Anna

    2009-11-01

    Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy characterised by accumulation of resistant prion protein (PrP(BSE)), neuronal loss, spongiosus and glial cell proliferation. In this study, properties of the extracellular matrix (ECM) were investigated in boTg110 transgenic mice over-expressing the bovine cellular prion protein (PrP(c)) and infected with BSE. Using immunohistochemistry with Wisteria floribunda agglutinin as a specific marker for perineuronal nets (PNNs) and antibodies against aggrecan and hyaluronic acid binding protein, loss of ECM was correlated with PrP(BSE) accumulation and activation of astrocytes and microglia. PrP(BSE) accumulation and glial cell activation were detected from the earliest stages of the disease and increased in the terminal stages. Decreases in PNNs, aggrecan and hyaluronic acid were observed only in the terminal stages and correlated with the distribution of PrP(BSE) and activated glial cells. This study suggests that the loss of PNNs, aggrecan and hyaluronic acid is a consequence of PrP(BSE) accumulation. Degradation of ECM in BSE may be due to secretion of degradative enzymes by activated glial cells.

  15. EU-approved rapid tests might underestimate bovine spongiform encephalopathy infection in goats.

    PubMed

    Meloni, Daniela; Bozzetta, Elena; Langeveld, Jan P M; Groschup, Martin H; Goldmann, Wilfred; Andrèoletti, Olivier; Lantier, Isabelle; Van Keulen, Lucien; Bossers, Alex; Pitardi, Danilo; Nonno, Romolo; Sklaviadis, Theodoros; Ingravalle, Francesco; Peletto, Simone; Colussi, Silvia; Acutis, Pier Luigi

    2017-03-01

    We report the diagnostic sensitivity of 3 EU-approved rapid tests (ELISAs; 1 from IDEXX and 2 from Bio-Rad) for the detection of transmissible spongiform encephalopathy diseases in goats. Ninety-eight goat brainstem samples were tested. All the rapid tests had 100% specificity and ≥80% sensitivity, with the IDEXX test significantly more sensitive than the 2 Bio-Rad tests. All tests detected 100% of samples from goats with clinical scrapie, but missed 8% (IDEXX) to 33% (Bio-Rad SG) of samples from preclinical goats. Importantly, only IDEXX picked up all samples from clinical bovine spongiform encephalopathy (BSE)-infected goats, whereas the other 2 rapid tests missed 15% (Bio-Rad SG) to 25% (Bio-Rad SAP). These results show that a fraction of preclinical scrapie infections are likely missed by EU surveillance, with sensitivity of detection strongly dependent on the choice of the rapid test. Moreover, a significant proportion of clinical BSE infections are underestimated by using either Bio-Rad test. Assuming that the same sensitivity on preclinical goats would also occur in BSE-infected goats, our data suggest that IDEXX is likely the most sensitive test for detecting preclinical field cases of BSE infection in goats, although with an 8% failure rate. These results raise some concerns about the reliability of current EU surveillance figures on BSE infection in goats.

  16. Generation of a persistently infected MDBK cell line with natural bovine spongiform encephalopathy (BSE).

    PubMed

    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.

  17. 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

  18. Increased Morbidity and Mortality in Domestic Animals Eating Dropped and Bitten Fruit in Bangladeshi Villages: Implications for Zoonotic Disease Transmission.

    PubMed

    Openshaw, John J; Hegde, Sonia; Sazzad, Hossain M S; Khan, Salah Uddin; Hossain, M Jahangir; Epstein, Jonathan H; Daszak, Peter; Gurley, Emily S; Luby, Stephen P

    2016-03-01

    We used data on feeding practices and domestic animal health gathered from 207 Bangladeshi villages to identify any association between grazing dropped fruit found on the ground or owners directly feeding bat- or bird-bitten fruit and animal health. We compared mortality and morbidity in domestic animals using a mixed effects model controlling for village clustering, herd size, and proxy measures of household wealth. Thirty percent of household heads reported that their animals grazed on dropped fruit and 20% reported that they actively fed bitten fruit to their domestic herds. Household heads allowing their cattle to graze on dropped fruit were more likely to report an illness within their herd (adjusted prevalence ratio 1.17, 95% CI 1.02-1.31). Household heads directly feeding goats bitten fruit were more likely to report illness (adjusted prevalence ratio 1.35, 95% CI 1.16-1.57) and deaths (adjusted prevalence ratio 1.64, 95% CI 1.13-2.4). Reporting of illnesses and deaths among goats rose as the frequency of feeding bitten fruit increased. One possible explanation for this finding is the transmission of bat pathogens to domestic animals via bitten fruit consumption.

  19. Increased morbidity and mortality in domestic animals eating dropped and bitten fruit in Bangladeshi villages: Implications for zoonotic disease transmission

    PubMed Central

    Openshaw, John J.; Hegde, Sonia; Sazzad, Hossain M. S.; Khan, Salah Uddin; Hossain, M. Jahangir; Epstein, Jonathan H.; Daszak, Peter; Gurley, Emily S.; Luby, Stephen P.

    2016-01-01

    We used data on feeding practices and domestic animal health gathered from 207 Bangladeshi villages to identify any association between grazing dropped fruit found on the ground or owners directly feeding bat or bird-bitten fruit and animal health. We compared mortality and morbidity in domestic animals using a mixed effects model controlling for village clustering, herd size, and proxy measures of household wealth. Thirty percent of household heads reported that their animals grazed on dropped fruit and 20% reported that they actively fed bitten fruit to their domestic herds. Household heads allowing their cattle to graze on dropped fruit were more likely to report an illness within their herd (adjusted prevalence ratio 1.17, 95% CI 1.02-1.31). Household heads directly feeding goats bitten fruit were more likely to report illness (adjusted prevalence ratio 1.35, 95% CI 1.16-1.57) and deaths (adjusted prevalence ratio 1.64, 95% CI 1.13-2.4). Reporting of illnesses and deaths among goats rose as the frequency of feeding bitten fruit increased. One possible explanation for this finding is the transmission of bat pathogens to domestic animals via bitten fruit consumption. PMID:26668032

  20. 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

    2007-09-05

    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.

  1. 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…

  2. 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…

  3. Transmission

    SciTech Connect

    Sugano, K.

    1988-12-27

    A transmission is described which consists of: an input shaft; an output shaft; a first planetary gear set including a first sun gear selectively connectable by a first clutch to the input shaft, a first carrier selectively connectable by a second clutch to the input shaft and a first ring gear connected to the output shaft. The first sun gear selectively held stationary by a first brake, the first carrier is allowed to rotate in the same forward direction as the input shaft when the second clutch is engaged, but prevented from rotating in a reverse direction opposite to the forward direction by a first one-way clutch, the first carrier being selectively held stationary by a second brake; a second planetary gear set including a second sun gear connected to the input shaft, a second carrier connected to the first ring gear and also the the output shaft, and a second ring gear.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  5. Atypical bovine spongiform encephalopathies, France, 2001-2007.

    PubMed

    Biacabe, Anne-Gaëlle; Morignat, Eric; Vulin, Johann; Calavas, Didier; Baron, Thierry G M

    2008-02-01

    In France, through exhaustive active surveillance, approximately 17.1 million adult cattle were tested for bovine spongiform encephalopathy from July 2001 through July 2007; approximately 3.6 million were >8 years of age. Our retrospective Western blot study of all 645 confirmed cases found that 7 were H-type and 6 were L-type.

  6. The infrequency of transmission of herpesviruses between humans and animals; postulation of an unrecognised protective host mechanism.

    PubMed

    Skinner, G R; Ahmad, A; Davies, J A

    2001-10-01

    The infrequency of natural transmission of herpesviruses between humans and animals is surprising as there is extensive contact between humans and non-human species with unequivocal evidence that host cells from non-susceptible species will support replication of herpesviruses which do not seem to naturally infect that species. This review examines natural cross-infections between human and other species and suggests that, firstly, it is possible that humans and animals do become asymptomatically or symptomatically cross-infected from other species, but the infection is not diagnosed or not diagnosable by conventional methods; secondly, an as yet unidentified novel mechanism(s) may operate to prevent infection using chemical, electrical or as yet unidentified pathways and may even be 'switched on' by exposure to the virus.

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

    PubMed

    Franz, Martin; Eiden, Martin; Balkema-Buschmann, Anne; Greenlee, Justin; Schatzl, Hermann; Fast, Christine; Richt, Jürgen; Hildebrandt, Jan-Peter; Groschup, Martin H

    2012-12-01

    Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease that mainly affects cattle. Transmission of BSE to humans caused a variant form of Creutzfeldt-Jakob disease. Following infection, the protease-resistant, disease-associated isoform of prion protein (PrP(Sc)) accumulates in the central nervous system and in other tissues. Many countries have defined bovine tissues that may contain prions as specified risk materials, which must not enter the human or animal food chains and therefore must be discarded. Ultrasensitive techniques such as protein misfolding cyclic amplification (PMCA) have been developed to detect PrP(Sc) when present in minuscule amounts that are not readily detected by other diagnostic methods such as immunohistochemistry or Western blotting. This study was conducted to determine when and where PrP(Sc) can be found by PMCA in cattle orally challenged with BSE. A total of 48 different tissue samples from four cattle infected orally with BSE at various clinical stages of disease were examined using a standardized PMCA protocol. The protocol used brain homogenate from bovine PrP transgenic mice (Tgbov XV) as substrate and three consecutive rounds of PMCA. Using this protocol, PrP(Sc) was found in the brain, spinal cord, nerve ganglia, optic nerve and Peyer's patches. The presence of PrP(Sc) was confirmed in adrenal glands, as well as in mesenteric lymph nodes - a finding that was reported recently by another group. Interestingly, additional positive results were obtained for the first time in the oesophagus, abomasum, rumen and rectum of clinically affected cattle.

  8. 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.

  9. [Recent topics on hepatitis E virus: emerging, zoonotic, and animal-to-human transmission in Japan].

    PubMed

    Mishiro, Shunji

    2004-12-01

    Hepatitis E is undoubtedly a zoonosis. Recent observations suggest that the zoonotic food-borne mode of transmission has played an important role in the spread of hepatitis E virus (HEV) among Japanese people (who in general likes eating everything uncooked or undercooked: Sushi, Sashimi, Tataki, Namagimo, Shabu-shabu, etc). Moreover, the situation seems to be worsening. Wild boar (and deer also) has recently been increasing in its number, becoming a more potent HEV reservoir to humans than before. Pork, replacing beef in people's recent fear of BSE, is being consumed increasingly, particularly in Hokkaido. It may be Japanese people that an effective HEV vaccine is most longed for by.

  10. Evaluation of the zoonotic potential of transmissible mink encephalopathy

    USDA-ARS?s Scientific Manuscript database

    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...

  11. [Interspecies transmission, adaptation to humans and pathogenicity of animal influenza viruses].

    PubMed

    Munier, S; Moisy, D; Marc, D; Naffakh, N

    2010-04-01

    The emergence in 2009 of a novel A(H1N1)v influenza virus of swine origin and the regular occurrence since 2003 of human cases of infection with A(H5N1) avian influenza viruses underline the zoonotic and pandemic potential of type A influenza viruses. Influenza viruses from the wild aquatic birds reservoir usually do not replicate efficiently in humans. Domestic poultry and swine can act as intermediate hosts for the acquisition of determinants that increase the potential of transmission and adaptation to humans, through the accumulation of mutations or by genetic reassortment. The rapid evolution of influenza viruses following interspecies transmission probably results from the selection of genetic variations that favor optimal interactions between viral proteins and cellular factors, leading to an increased multiplication potential and a better escape to the host antiviral response. Whereas influenza viruses usually cause asymptomatic infections in wild aquatic birds, they may be highly pathogenic in other species. Molecular determinants of host-specificity and pathogenesis have been identified in most viral genes, notably in genes that encode viral surface glycoproteins, proteins involved in the viral genome replication, and proteins that counteract the host immune response. However, our knowledge of these numerous and interdependant determinants remains incomplete, and the molecular mechanisms involved are still to be understood.

  12. Circulation of bovine ephemeral fever in the Middle East--strong evidence for transmission by winds and animal transport.

    PubMed

    Aziz-Boaron, Orly; Klausner, Ziv; Hasoksuz, Mustafa; Shenkar, Jenny; Gafni, Ohad; Gelman, Boris; David, Dan; Klement, Eyal

    2012-08-17

    Bovine ephemeral fever virus (BEFV) is an economically important arbovirus of cattle. The main routes of its transmission between countries and continents are not completely elucidated. This study aimed to explore BEFV transmission in the Middle-East. A phylogenetic analysis was performed on the gene encoding the G protein of BEFV isolates from Israel from 2000 and 2008 with isolates from Turkey (2008), Egypt (2005), Australia (1968-1998) and East Asia (1966-2004). Calf sera collected during the years 2006-2007 were tested by serum neutralization in order to explore for recent exposure to BEFV before 2008. These were followed by a meteorological analysis, aimed to reveal movement of air parcels into Israel in the two weeks preceding the first case of BEF in Israel in 2008. The 2008 Israeli and Turkish isolates showed 99% identity and formed a new cluster with the 2000 Israeli isolate. The serological survey showed no new exposure to BEFV during 2006 and 2007. These results coincided with the meteorological analysis, which revealed that air parcels originating in Southern Turkey had reached the location of outbreak onset in Israel nine days before the discovery of the index case. The Egyptian isolate clustered phylogenetically with the Taiwanese isolates, coinciding with data on importation of cattle from China to the Middle East in the year preceding the isolation of the Egyptian isolates. These results suggest that both winds and animal transport may have an important role in trans-boundary transmission of BEFV.

  13. 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.

  14. 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

  15. 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

  16. 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

    USDA-ARS?s Scientific Manuscript database

    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...

  17. IncFII Conjugative Plasmid-Mediated Transmission of blaNDM-1 Elements among Animal-Borne Escherichia coli Strains.

    PubMed

    Lin, Dachuan; Xie, Miaomiao; Li, Ruichao; Chen, Kaichao; Chan, Edward Wai-Chi; Chen, Sheng

    2017-01-01

    This study aims to investigate the prevalence and transmission dynamics of the blaNDM-1 gene in animal Escherichia coli strains. Two IncFII blaNDM-1-encoding plasmids with only minor structural variation in the MDR region, pHNEC46-NDM and pHNEC55-NDM, were found to be responsible for the transmission of blaNDM-1 in these strains. The blaNDM-1 gene can be incorporated into plasmids and stably inherited in animal-borne E. coli strains that can be maintained in animal gut microflora even without carbapenem selection pressure. Copyright © 2016 American Society for Microbiology.

  18. 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

  19. 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.

  20. Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice.

    PubMed

    Jaumain, Emilie; Quadrio, Isabelle; Herzog, Laetitia; Reine, Fabienne; Rezaei, Human; Andréoletti, Olivier; Laude, Hubert; Perret-Liaudet, Armand; Haïk, Stéphane; Béringue, Vincent

    2016-12-01

    Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrP(C)) and the infecting pathological PrP assemblies (PrP(Sc)) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrP(C) and in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrP(Sc) signatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD. Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. [Analysis of risk factors associated with bovine spongiform encephalopathy in Argentina].

    PubMed

    Cané, B G; Gimeno, E J; Manetti, J C; Van Gelderen, C; Ulloa, E; Schudel, A A

    1993-12-01

    Epidemiological studies conducted in the United Kingdom have revealed the risk factors involved in the epidemic of bovine spongiform encephalopathy (BSE). This has facilitated a detailed study of risk factors associated with the possible introduction of BSE into Argentina. An analysis has been made of the numbers and geographical distribution of cattle in the country, the structure of the Veterinary Services responsible for controlling animal diseases, the way in which cattle and sheep are slaughtered, and the use of slaughter waste in the feed industry. The results of this analysis form the basis of a discussion of whether scrapie or BSE could become endemic in Argentina through contaminated feed or another route. The authors conclude that Argentina may be regarded as free from BSE, and that the importation of infected bovines is the sole potential risk for introduction of BSE in the future.

  2. 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.

  3. The Leeuwenhoek Lecture 2001. Animal origins of human infectious disease.

    PubMed

    Weiss, R A

    2001-06-29

    Since time immemorial animals have been a major source of human infectious disease. Certain infections like rabies are recognized as zoonoses caused in each case by direct animal-to-human transmission. Others like measles became independently sustained with the human population so that the causative virus has diverged from its animal progenitor. Recent examples of direct zoonoses are variant Creutzfeldt-Jakob disease arising from bovine spongiform encephalopathy, and the H5N1 avian influenza outbreak in Hong Kong. Epidemics of recent animal origin are the 1918-1919 influenza pandemic, and acquired immune deficiency syndrome caused by human immunodeficiency virus (HIV). Some retroviruses jump into and out of the chromosomal DNA of the host germline, so that they oscillate between being inherited Mendelian traits or infectious agents in different species. Will new procedures like animal-to-human transplants unleash further infections? Do microbes become more virulent upon cross-species transfer? Are animal microbes a threat as biological weapons? Will the vast reservoir of immunodeficient hosts due to the HIV pandemic provide conditions permissive for sporadic zoonoses to take off as human-to-human transmissible diseases? Do human infections now pose a threat to endangered primates? These questions are addressed in this lecture.

  4. Abnormal regulation of TSG101 in mice with spongiform neurodegeneration.

    PubMed

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

    2009-10-01

    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.

  5. 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.

  6. Gene expression in the medulla following oral infection of cattle with bovine spongiform encephalopathy.

    PubMed

    Almeida, Luciane M; Basu, Urmila; Khaniya, Bina; Taniguchi, Masaaki; Williams, John L; Moore, Stephen S; Guan, Le Luo

    2011-01-01

    The identification of variations in gene expression in response to bovine spongiform encephalopathy (BSE) may help to elucidate the mechanisms of neuropathology and prion replication and discover biomarkers for disease. In this study, genes that are differentially expressed in the caudal medulla tissues of animals infected with different doses of PrP(BSE) at 12 and 45 mo post infection were compared using array containing 24,000 oligonucleotide probes. Data analysis identified 966 differentially expressed (DE) genes between control and infected animals. Genes identified in at least two of four experiments (control versus 1-g infected animals at 12 and 45-mo; control versus 100-g infected animals at 12 and 45 mo) were considered to be the genes that may be associated with BSE disease. From the 176 DE genes associated with BSE, 84 had functions described in the Gene Ontology (GO) database. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of 14 genes revealed that prion infection may cause dysfunction of several different networks, including extracellular matrix (ECM), cell adhesion, neuroactive ligand-receptor interaction, complement and coagulation cascades, MAPK signaling, neurodegenerative disorder, SNARE interactions in vesicular transport, and the transforming growth factor (TGF) beta signaling pathways. The identification of DE genes will contribute to a better understanding of the molecular mechanisms of neuropathology in bovine species. Additional studies on larger number of animals are in progress in our laboratory to investigate the roles of these DE genes in pathogenesis of BSE.

  7. Development and transmission of antimicrobial resistance among Gram-negative bacteria in animals and their public health impact.

    PubMed

    Mukerji, Shewli; O'Dea, Mark; Barton, Mary; Kirkwood, Roy; Lee, Terence; Abraham, Sam

    2017-02-28

    Gram-negative bacteria are known to cause severe infections in both humans and animals. Antimicrobial resistance (AMR) in Gram-negative bacteria is a major challenge in the treatment of clinical infections globally due to the propensity of these organisms to rapidly develop resistance against antimicrobials in use. In addition, Gram-negative bacteria possess highly efficient mechanisms through which the AMR can be disseminated between pathogenic and commensal bacteria of the same or different species. These unique traits of Gram-negative bacteria have resulted in evolution of Gram-negative bacterial strains demonstrating resistance to multiple classes of antimicrobials. The evergrowing resistance issue has not only resulted in limitation of treatment options but also led to increased treatment costs and mortality rates in humans and animals. With few or no new antimicrobials in production to combat severe life-threatening infections, AMR has been described as the one of the most severe, long-term threats to human health. Aside from overuse and misuse of antimicrobials in humans, another factor that has exacerbated the emergence of AMR in Gram-negative bacteria is the veterinary use of antimicrobials that belong to the same classes considered to be critically important for treating serious life-threatening infections in humans. Despite the fact that development of AMR dates back to before the introduction of antimicrobials, the recent surge in the resistance towards all available critically important antimicrobials has emerged as a major public health issue. This review thus focuses on discussing the development, transmission and public health impact of AMR in Gram-negative bacteria in animals.

  8. Disease characteristics of bovine spongiform encephalopathy following inoculation into mice via three different routes.

    PubMed

    Vickery, Christopher M; Beck, Katy E; Simmons, Marion M; Hawkins, Stephen A C; Spiropoulos, John

    2013-10-01

    Mouse-adapted transmissible spongiform encephalopathy (TSE) strains are routinely distinguished based on reproducible disease characteristics in a given mouse line following inoculation via a consistent route. We investigated whether different administration routes (oral, intragastric (i.g.) and intracerebral (i.c.)) can alter the disease characteristics in IM mice after serial dilution of a stabilized mouse-adapted bovine spongiform encephalopathy (BSE) strain (301V). In addition, the infectivity of distal ileum and mesenteric lymph nodes (ln) sampled at three time points (35 days postinoculation (dpi), 70 dpi and terminal disease) after i.g. inoculation of 301V strain was assessed in mice by i.c. challenge. Strain characteristics were assessed according to standard methodology and PrP(Sc) immunohistochemistry deposition patterns. Mean incubation periods were prolonged following oral or i.g. inoculations compared to the i.c. route. Lesion profiles following i.c. challenges were elevated compared to i.g. and oral routes although vacuolation in the dorsal medulla was consistently high irrespective of the route of administration. Nevertheless, the same PrP(Sc) deposition pattern was associated with each route of administration. Distal and mesenteric ln infectivity was detected as early as 35 dpi and displayed consistent lesion profiles and PrP(Sc) deposition patterns. Our data suggest that although 301V retained its properties, some phenotypic parameters were affected by the route of inoculation. We conclude that bioassay data should be interpreted carefully and should be standardized for route of inoculation. © 2013 Crown Copyright. International Journal of Experimental Pathology published by John Wiley & Sons Ltd.

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  10. Comparison of Transmissible Mink Encephalopathy Isolates in Raccoons

    USDA-ARS?s Scientific Manuscript database

    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...

  11. 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

  12. 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.

  13. [Risk assessment for importing bovine spongiform encephalopathy (BSE)].

    PubMed

    Hörnlimann, B; Guidon, D; Griot, C

    1994-07-01

    Since the occurrence of bovine spongiform encephalopathy (BSE) in Switzerland in 1990, extensive epidemiological investigations and risk factor analyses were carried out. In this study, statistical data on meat and bone meal traded from 1985 to 1989 were analysed addressing the following questions: i) what amount of meat and bone meal was exported from Great Britain (GB) and where to and ii) what amount of meat and bone meal was imported into Switzerland and where from? The findings led to the hypothesis that imported material potentially infected with scrapie-like agents was the cause for BSE in Switzerland.

  14. Safety evaluation for a biodiesel process using prion-contaminated animal fat as a source.

    PubMed

    Seidel, Björn; Alm, Martin; Peters, Rainer; Kördel, Werner; Schäffer, Andreas

    2006-03-01

    Due to the bovine spongiform encephalopathy (BSE), specified risk material (SRM) as well as animal meat and bone meal (MBM) are banned from the food and feed chain because of a possible infection with pathogenic prions (PrP(Sc)). Nowadays, prions are widely accepted to be responsible for TSE(transmissible spongiform encephalopathies)-caused illnesses like BSE and scrapie, and especially for the occurrence of the new variant of CJD in humans. Presently, SRM and MBM are burnt under high temperatures to avoid any hazards for humans, animals or the environment. The aim of this study was to evaluate a method using animal fat separated from Category I material which includes SRM and the carcasses of TSE-infected animals, or animals suspected of being infected with TSE, as a source for producing biodiesel by transesterification, analogous to the biodiesel process using vegetable oil. For this purpose, animal fat was spiked with scrapie-infected hamster brain equivalents--as representative for a TSE-infected animal--and the biodiesel manufacturing process was downscaled and performed under lab-scale conditions. The results analysed by Western blotting showed clearly that almost each single step of the process leads to a significant reduction of the concentration of the pathogenic prion protein (PrP(Sc)) in the main and side-products. The data revealed that the biodiesel production, even from material with a high concentration of pathogenic prions, can be considered as safe. The obtained results indicated that biodiesel produced from prion-contaminated fat was safe under the tested process conditions. However, it has to be pointed out that the results cannot be generalized because a different process control using other conditions may lead to different results and then has to be analysed independently. It is clear that the production of biodiesel from high risk material represents a more economic usage than the combustion of such material.

  15. Extent of Mycobacterium bovis transmission among animals of dairy and beef cattle and deer farms in South Korea determined by variable-number tandem repeats typing.

    PubMed

    Je, Sungmo; Ku, Bok Kyung; Jeon, Bo-Young; Kim, Jae-Myoung; Jung, Suk-Chan; Cho, Sang-Nae

    2015-04-17

    Identifying sources of Mycobacterium bovis transmission would be essential for establishing effective control programs of bovine tuberculosis (TB), a major zoonosis threatening human health worldwide. As an effort to determine the extent of M. bovis transmission among dairy and beef cattle and deer populations, a mycobacterial interspersed repetitive units (MIRU)-variable-number tandem repeats (VNTR) typing method was employed for analysis of 131 M. bovis isolates from 59 Holstein dairy cattle, 39 Korean beef cattle, and 33 deer. Of 31 MIRU-VNTR markers, 15 showed allelic diversity. The most discriminatory locus for M. bovis isolates was VNTR 3336 (h=0.59) followed by QUB 26, MIRU 31, VNTR 2401, and VNTR 3171 which showed high discriminatory power (h=0.43). The combined VNTR loci had an allelic diversity of 0.83. On the basis of the VNTR profiles of 30 VNTR loci, 24 genotypes were identified, and two genotypes were highly prevalent among all M. bovis isolates (33.6% and 19.1%, respectively), thus indicating that more than 50% of the isolates shared common molecular characteristics. Six additional genotypes were common in 2 of the 3 animal species, suggesting a wide interspecies transmission of M. bovis. This study thus demonstrates that MIRU-VNTR typing is useful in differentiation of M. bovis isolates and that M. bovis transmission occurs frequently among farmed animal species, highlighting the importance of bovine TB control programs in different animal species which are often raised in the same villages.

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  17. 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

  18. 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. © 2015 Zoonoses and Public Health © 2015 Her Majesty the Queen in Right of Canada Reproduced with the permission of the Minister of the Public Health Agency of Canada.

  19. Bovine spongiform encephalopathy: is it time to relax BSE-related measures in the context of international trade?

    PubMed

    Matthews, D; Adkin, A

    2011-04-01

    Bovine spongiform encephalopathy (BSE) has presented serious challenges to both the World Organisation for Animal Health and national governments, in defining and implementing appropriate national control measures, and in agreeing trade rules that permit safe trade in cattle and bovine products. Precautionary trade rules were initially necessary, based upon the science of sheep scrapie, but research into BSE later enabled BSE-specific trade rules to be developed. As a result, current rules on trade are underpinned by a sound body of knowledge on BSE. Declining epidemics in most affected countries confirm the appropriateness of current precautions. Nevertheless, risk is primarily dependent on the prevalence of infection with BSE. In the face of low prevalence scenarios, certain precautionary measures in the Terrestrial Animal Health Code may now be considered excessive. A thorough review is therefore deemed appropriate.

  20. Isolation from Cattle of a Prion Strain Distinct from That Causing Bovine Spongiform Encephalopathy

    PubMed Central

    Béringue, Vincent; Reine, Fabienne; Laï, Thanh Lan; Chenais, Nathalie; Tilly, Gaëlle; Biacabé, Anne-Gaëlle; Baron, Thierry; Vilotte, Jean-Luc; Laude, Hubert

    2006-01-01

    To date, bovine spongiform encephalopathy (BSE) and its human counterpart, variant Creutzfeldt-Jakob disease, have been associated with a single prion strain. This strain is characterised by a unique and remarkably stable biochemical profile of abnormal protease-resistant prion protein (PrPres) isolated from brains of affected animals or humans. However, alternate PrPres signatures in cattle have recently been discovered through large-scale screening. To test whether these also represent separate prion strains, we inoculated French cattle isolates characterised by a PrPres of higher apparent molecular mass—called H-type—into transgenic mice expressing bovine or ovine PrP. All mice developed neurological symptoms and succumbed to these isolates, showing that these represent a novel strain of infectious prions. Importantly, this agent exhibited strain-specific features clearly distinct from that of BSE agent inoculated to the same mice, which were retained on further passage. Moreover, it also differed from all sheep scrapie isolates passaged so far in ovine PrP-expressing mice. Our findings therefore raise the possibility that either various prion strains may exist in cattle, or that the BSE agent has undergone divergent evolution in some animals. PMID:17054396

  1. PRNP and SPRN genes polymorphism in atypical bovine spongiform encephalopathy cases diagnosed in Polish cattle.

    PubMed

    Gurgul, Artur; Polak, Mirosław Paweł; Larska, Magdalena; Słota, Ewa

    2012-08-01

    Polymorphisms in the coding region of the prion protein gene (PRNP) have been associated with the susceptibility and incubation period of prion diseases in humans and sheep. However, polymorphisms in this part of the bovine PRNP gene do not affect the classical bovine spongiform encephalopathy (BSE) susceptibility in cattle. Studies carried out in Germany have shown that insertion/deletion-type polymorphisms located in the promoter region of the bovine prion gene are possible genetic factors modulating BSE susceptibility by changing the level of PRNP expression. No such association was observed for atypical BSE cases; however, due to the rare nature of the disease, these results should be confirmed. Additionally, a single nonsynonymous mutation in PRNP codon 211 (E211K) was described in one H-type BSE case in the USA; however, it was not found in any other cases. Here, we performed genetic characterization of PRNP promoter indel variations and determined the polymorphism of open reading frames (ORFs) of PRNP and bovine prion-like Shadoo (SPRN) genes in six Polish atypical BSE cases and compared these results to the population of clinically healthy Polish Holstein cattle. No potentially pathogenic mutations were found in the PRNP ORF in atypical BSE-affected cattle, but our study showed a high frequency of deletions at the indel loci of PRNP promoter in these animals. Additionally, a rare sequence variation in the SPRN protein-coding sequence was found in one L-type atypical BSE-affected animal.

  2. Neuropathological changes in auditory brainstem nuclei in cattle with experimentally induced bovine spongiform encephalopathy.

    PubMed

    Fukuda, S; Okada, H; Arai, S; Yokoyama, T; Mohri, S

    2011-01-01

    Bovine spongiform encephalopathy (BSE) is characterized by the appearance of spongy lesions in the brain, particularly in the brainstem nuclei. This study evaluated the degenerative changes observed in the central auditory brainstem of BSE-challenged cattle. The neuropathological changes in the auditory brainstem nuclei were assessed by determining the severity of vacuolation and the presence of disease-associated prion protein (PrP(Sc)). Sixteen female Holstein-Friesian calves, 2-4 months of age, were inoculated intracerebrally with BSE agent. BSE-challenged animals developed the characteristic clinical signs of BSE approximately 18 months post inoculation (mpi) and advanced neurological signs after 22 mpi. Before the appearance of clinical signs (i.e. at 3, 10, 12 and 16 mpi), vacuolar change was absent or mild and PrP(Sc) deposition was minimal in the auditory brainstem nuclei. The two cattle sacrificed at 18 and 19 mpi had no clinical signs and showed mild vacuolar degeneration and moderate amounts of PrP(Sc) accumulation in the auditory brainstem pathway. In the animals challenged with BSE agent that developed clinical sings (i.e. after 20 mpi), spongy changes were more prominent in the nucleus of the inferior colliculus compared with the other nuclei of the auditory brainstem and the medial geniculate body. Neuropathological changes characterized by spongy lesions accompanied by PrP(Sc) accumulation in the auditory brainstem nuclei of BSE-infected cattle may be associated with hyperacusia. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges.

    PubMed

    Konold, Timm; Bone, Gemma E; Clifford, Derek; Chaplin, Melanie J; Cawthraw, Saira; Stack, Michael J; Simmons, Marion M

    2012-03-08

    The majority of atypical bovine spongiform encephalopathy (BSE) cases so far identified worldwide have been detected by active surveillance. Consequently the volume and quality of material available for detailed characterisation is very limiting. Here we report on a small transmission study of both atypical forms, H- and L-type BSE, in cattle to provide tissue for test evaluation and research, and to generate clinical, molecular and pathological data in a standardised way to enable more robust comparison of the two variants with particular reference to those aspects most relevant to case ascertainment and confirmatory diagnosis within existing regulated surveillance programmes. Two groups of four cattle, intracerebrally inoculated with L-type or H-type BSE, all presented with a nervous disease form with some similarities to classical BSE, which progressed to a more dull form in one animal from each group. Difficulty rising was a consistent feature of both disease forms and not seen in two BSE-free, non-inoculated cattle that served as controls. The pathology and molecular characteristics were distinct from classical BSE, and broadly consistent with published data, but with some variation in the pathological characteristics. Both atypical BSE types were readily detectable as BSE by current confirmatory methods using the medulla brain region at the obex, but making a clear diagnostic distinction between the forms was not consistently straightforward in this brain region. Cerebellum proved a more reliable sample for discrimination when using immunohistochemistry. The prominent feature of difficulty rising in atypical BSE cases may explain the detection of naturally occurring cases in emergency slaughter cattle and fallen stock. Current confirmatory diagnostic methods are effective for the detection of such atypical cases, but consistently and correctly identifying the variant forms may require modifications to the sampling regimes and methods that are currently in use.

  4. Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges

    PubMed Central

    2012-01-01

    Background The majority of atypical bovine spongiform encephalopathy (BSE) cases so far identified worldwide have been detected by active surveillance. Consequently the volume and quality of material available for detailed characterisation is very limiting. Here we report on a small transmission study of both atypical forms, H- and L-type BSE, in cattle to provide tissue for test evaluation and research, and to generate clinical, molecular and pathological data in a standardised way to enable more robust comparison of the two variants with particular reference to those aspects most relevant to case ascertainment and confirmatory diagnosis within existing regulated surveillance programmes. Results Two groups of four cattle, intracerebrally inoculated with L-type or H-type BSE, all presented with a nervous disease form with some similarities to classical BSE, which progressed to a more dull form in one animal from each group. Difficulty rising was a consistent feature of both disease forms and not seen in two BSE-free, non-inoculated cattle that served as controls. The pathology and molecular characteristics were distinct from classical BSE, and broadly consistent with published data, but with some variation in the pathological characteristics. Both atypical BSE types were readily detectable as BSE by current confirmatory methods using the medulla brain region at the obex, but making a clear diagnostic distinction between the forms was not consistently straightforward in this brain region. Cerebellum proved a more reliable sample for discrimination when using immunohistochemistry. Conclusions The prominent feature of difficulty rising in atypical BSE cases may explain the detection of naturally occurring cases in emergency slaughter cattle and fallen stock. Current confirmatory diagnostic methods are effective for the detection of such atypical cases, but consistently and correctly identifying the variant forms may require modifications to the sampling regimes and

  5. Spongiform encephalopathy in an arabian oryx (Oryx leucoryx) and a greater kudu (Tragelaphus strepsiceros)

    PubMed

    Kirkwood, J K; Wells, G A; Wilesmith, J W; Cunningham, A A; Jackson, S I

    1990-10-27

    Clinical, pathological and epidemiological details of scrapie-like encephalopathies are described in an arabian oryx and a greater kudu. Clinical signs included ataxia and loss of condition with a short, progressive clinical course (22 and three days, respectively). Histopathological examination of the brains revealed spongiform encephalopathy characteristic of that observed in scrapie and bovine spongiform encephalopathy (BSE). It seems probable that these cases have a common aetiology with BSE. Scrapie-like spongiform encephalopathies have now been described in five species of exotic artiodactyls in Britain indicating a, hitherto inapparent, wider range of ruminant species as natural hosts for these diseases.

  6. Genomic characterization of a rotavirus G8P[1] detected in a child with diarrhea reveal direct animal-to-human transmission.

    PubMed

    Martinez, Magaly; Phan, Tung Gia; Galeano, Maria Eugenia; Russomando, Graciela; Parreno, Viviana; Delwart, Eric; Parra, Gabriel I

    2014-10-01

    Group A rotavirus is a major cause of severe gastroenteritis in children and young animals. During a retrospective analysis of samples collected from Paraguayan children under 5 years old with diarrhea, and previously negative for rotavirus and norovirus, we detected the presence of bovine rotavirus sequences by viral metagenomics. Nucleic acid was extracted direct from stool sample and determined to be G8P[1]. The genomic analyzes revealed that the strain presents an Artiodactyl-like genome (G8-P[1]-I2-R2-C2-M1-Ax-N2-T6-E12-H3) suggesting a direct animal-to-human transmission.

  7. 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.

  8. 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

    2016-08-24

    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.

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

    PubMed Central

    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.

  11. 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

    2016-03-07

    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.

  12. 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

  13. Distribution of abnormal prion protein in a sheep affected with L-type bovine spongiform encephalopathy.

    PubMed

    Matsuura, Y; Iwamaru, Y; Masujin, K; Imamura, M; Mohri, S; Yokoyama, T; Okada, H

    2013-07-01

    To investigate the topographical distribution and patterns of deposition of immunolabelled abnormal prion protein (PrP(Sc)), interspecies transmission of atypical L-type bovine spongiform encephalopathy (BSE) to Cheviot ewes (ARQ/ARQ genotype) was performed. L-type BSE was successfully transmitted via the intracerebral route to a ewe, with an incubation period of 1,562 days. Minimal vacuolar change was detected in the basal ganglia, thalamus and brainstem, and PrP(Sc) accumulated throughout the brain. The L-type BSE-affected sheep was characterized by conspicuous fine particulate deposits in the neuropil, particulate and/or granular intraneuronal and intraglial deposits, and the absence of PrP(Sc) plaques or stellate deposits. In addition, immunohistochemical and western blot analyses revealed that PrP(Sc) accumulation was present in peripheral nervous tissues (including the trigeminal ganglia and dorsal root ganglion) and adrenal glands, but was absent in lymphoid tissues. These results suggest that L-type BSE has distinct and distinguishable characteristics as well as PrP(Sc) tissue tropism in sheep. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Experimental challenge of cattle with German atypical bovine spongiform encephalopathy (BSE) isolates.

    PubMed

    Balkema-Buschmann, A; Ziegler, U; McIntyre, L; Keller, M; Hoffmann, C; Rogers, R; Hills, B; Groschup, M H

    2011-01-01

    For almost two decades after the discovery of the first bovine spongiform encephalopathy (BSE) case, it was generally accepted that only one BSE strain existed globally. However, in 2004, two novel BSE forms (L-type and H-type) were separately identified in two different European Member States, forms that differed from the classical (C-type) form by their biochemical properties and by the pattern of PrP(Sc) deposition as determined by immunohistochemistry (IHC). 60 atypical BSE cases have been identified worldwide as of November 2010, including one H- and one L-type BSE case each in Germany. However, it was not known whether the biological properties (pathogenesis and agent distribution, as well as transmissibility to other species) of these novel forms were the same as in classical BSE cases. Eleven calves were thus challenged intracranially, five with the German H-type and six with German L-type BSE cases. The experimental design and the clinical studies, followed by laboratory testing, are described in this manuscript.

  15. Experimental transmission of chronic wasting disease (CWD) from elk and white-tailed deer to fallow deer by intracerebral route: Final report

    PubMed Central

    Hamir, Amir N.; Greenlee, Justin J.; Nicholson, Eric M.; Kunkle, Robert A.; Richt, Juergen A.; Miller, Janice M.; Hall, Mark

    2011-01-01

    Final observations on experimental transmission of chronic wasting disease (CWD) from elk (Cervus elaphus nelsoni) and white-tailed deer (Odocoileus virginianus) to fallow deer (Dama dama) are reported herein. During the 5-year study, 13 fawns were inoculated intracerebrally with CWD-infected brain material from white-tailed deer (n = 7; Group A) or elk (n = 6; Group B), and 3 other fawns were kept as uninoculated controls (Group C). As described previously, 3 CWD-inoculated deer were euthanized at 7.6 mo post-inoculation (MPI). None revealed presence of abnormal prion protein (PrPd) in their tissues. At 24 (Group A) and 26 (Group B) MPI, 2 deer were necropsied. Both animals had a small focal accumulation of PrPd in their midbrains. Between 29 and 37 MPI, 3 other deer (all from Group A) were euthanized. The 5 remaining deer became sick and were euthanized between 51 and 60 MPI (1 from Group A and 4 from Group B). Microscopic lesions of spongiform encephalopathy (SE) were observed in only these 5 animals; however, PrPd was detected in tissues of the central nervous system by immunohistochemistry, Western blot, and by commercial rapid test in all animals that survived beyond 24 MPI. This study demonstrates that intracerebrally inoculated fallow deer not only amplify CWD prions, but also develop lesions of spongiform encephalopathy. PMID:21731188

  16. Melanoma-Associated Spongiform Scleropathy in Oculodermal Melanocytosis with Primary Orbital Melanoma

    PubMed Central

    Ranjit, Roshni U.; Leyngold, Ilya M.; Margo, Curtis E.

    2016-01-01

    Purpose To describe spongiform scleropathy in a patient with oculodermal melanosis and without evidence of uveal melanoma. Methods Clinical-pathological correlation conducted in compliance with HIPPA (Health Insurance Privacy and Portability Act) regulations. Results Melanoma-associated spongiform scleropathy was an incidental finding in an 87-year-old woman with oculodermal melanocytosis treated for primary orbital melanoma. All previously reported cases of this scleropathy have been associated with uveal melanoma. Conclusions The mechanism of scleral degeneration in melanoma-associated spongiform scleropathy is unknown, and its clinical and prognostic significance is speculative. This is the first case of a so-called melanoma-associated spongiform scleropathy reported in an eye without uveal melanoma. PMID:27843909

  17. Intravenous Heroin-Associated Delayed Spongiform Leukoencephalopathy: Case Report and Reviews of the Literature.

    PubMed

    Pirompanich, Pattarin; Chankrachang, Siwaporn

    2015-07-01

    Heroin-associated spongiform leukoencephalopathy is a rare, and sometimes fatal, condition usually caused by vapor inhalation of heroin. The authors report a 41-year-old man who was diagnosed with delayed spongiform leukoencephalopathy three weeks after injecting heroin intravenously. He had been admitted to another hospital due to acute heroin overdose, which had occurred four hours after intravenous injection of an unknown amount of heroin. His clinical condition showed progressive improvement and he was discharged 12 days after admission. Three weeks after this episode, his cognitive functioning declined. Akinetic mutism, spasticity and hyperreflexia of all extremities were observed. Electroencephalography (EEG) and imaging of the brain showed typical characteristics of spongiform leukoencephalopathy. The three and six-month follow-up of the patient showed clinical improvement and this was corroborated through EEG measures and brain imaging. The discussion summarizes eight previously reported cases of intravenous heroin associated spongiform leukoencephalopathy and compares them to the authors'case.

  18. 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 on...

  19. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. On the Question of Sporadic or Atypical Bovine Spongiform Encephalopathy and Creutzfeldt-Jakob Disease

    PubMed Central

    McShane, Lisa M.; Zanusso, Gianluigi; Detwiler, Linda

    2006-01-01

    Strategies to investigate the possible existence of sporadic bovine spongiform encephalopathy (BSE) require systematic testing programs to identify cases in countries considered to have little or no risk of orally acquired disease or to detect a stable occurrence of atypical cases in countries in which orally acquired disease is disappearing. To achieve 95% statistical confidence that the prevalence for sporadic BSE is no greater than 1 per million (i.e., the annual incidence of sporadic Creutzfeldt-Jakob disease [CJD] in humans) would require negative tests in 3 million randomly selected older cattle. A link between BSE and sporadic CJD has been suggested on the basis of laboratory studies but is unsupported by epidemiologic observation. Such a link might yet be established by the discovery of a specific molecular marker or of particular combinations of trends over time of typical and atypical BSE and various subtypes of sporadic CJD, as their numbers are influenced by a continuation of current public health measures that exclude high-risk bovine tissues from the animal and human food chains. PMID:17326930

  2. Spatial analysis of bovine spongiform encephalopathy in Galicia, Spain (2000-2005).

    PubMed

    Allepuz, A; López-Quílez, A; Forte, A; Fernández, G; Casal, J

    2007-05-16

    In Spain, the first bovine spongiform encephalopathy (BSE) case was detected in 2000 in a cow born in the Galicia region (Northwestern Spain). From then and until October 2005, 590 cases were detected, 223 of them in Galicia. In 1994, meat and bone meal (MBM) was banned on ruminant feed and, in 1996, an EU decision mandating an overall change in MBM processing was implemented. This decision was gradually applied in the territory and not enforced before July 1998. The objective of this study was to explore clustering of BSE cases and estimate the standard incidence ratio (SIR) of BSE in Galicia. Our study was based on the BSE cases detected during the surveillance period 2000-2005 in the Galicia region. These cases were divided, based on birth date, into two periods: animals born from 1994 to July 1998, and those born after July 1998. We tested the role of cross-contamination on the geographical SIR distribution for both periods. Hierarchical Bayesian models were used to model the overdispersion and lack of independence of the SIR estimates. The geographical distribution of the standard incidence ratio of BSE between both periods was different. In the second period, the SIR was reduced in some areas. The reduction in these areas could be attributable to the changes in the processing of MBM. We did not find any statistical link between the poultry population and the standard incidence ratio, but pig population had a positive effect.

  3. 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.

  4. 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

    2011-10-25

    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.

  5. Transmissibility of caprine scrapie in ovine transgenic mice

    USDA-ARS?s Scientific Manuscript database

    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...

  6. The presence of disease-associated prion protein in skeletal muscle of cattle infected with classical bovine spongiform encephalopathy.

    PubMed

    Okada, Hiroyuki; Miyazawa, Kohtaro; Fukuda, Shigeo; Iwamaru, Yoshifumi; Imamura, Morikazu; Masujin, Kentaro; Matsuura, Yuichi; Fujii, Takashi; Fujii, Kei; Kageyama, Soichi; Yoshioka, Miyako; Murayama, Yuichi; Yokoyama, Takashi

    2014-01-01

    The aim of this study was to investigate the presence of disease-associated prion protein (PrP(Sc)) in the skeletal muscle of cattle infected with classical bovine spongiform encephalopathy (C-BSE). The study was carried out systematically in 12 different muscle samples from 43 (3 field and 40 experimental) cases of C-BSE; however, muscle spindles were not available in many of these cases. Therefore, analysis became restricted to a total of 31 muscles in 23 cattle. Even after this restriction, low levels of PrP(Sc) were detected in the muscle spindles of the masseter, intercostal, triceps brachii, psoas major, quadriceps femoris and semitendinosus muscles from 3 field and 6 experimental clinical-stage cases. The present data indicate that small amounts of PrP(Sc) are detectable by immunohistochemistry in the skeletal muscles of animals terminally affected with C-BSE.

  7. Longitudinal molecular epidemiological analysis of feline calicivirus infection in an animal shelter: a model for investigating calicivirus transmission within high-density, high-turnover populations.

    PubMed

    Coyne, Karen P; Edwards, David; Radford, Alan D; Cripps, Peter; Jones, David; Wood, James L N; Gaskell, Rosalind M; Dawson, Susan

    2007-10-01

    The control of outbreaks of calicivirus infection in high-density, high-throughput populations is a challenge to both human and veterinary medicine. In such populations, the prevalence of infection is, in part, dependent on the levels of biosecurity and how this affects virus transmission. Here we show how longitudinal analysis of feline calicivirus (FCV) infection in an animal rescue shelter can be used as a model to examine the dynamics of calicivirus transmission and evolution in such environments. FCV was isolated from 33 of 116 cats sampled over a 15-month period (overall prevalence, 28%). Sequence analysis of the immunodominant variable regions of the viral capsid gene identified 16 strains circulating in the shelter, with no single strain appearing to predominate. The majority of these strains were introduced into the shelter from the community and did not appear to be transmitted within the population. However, for three of these strains, putative transmission events within the shelter were identified. The rates of evolution within hypervariable regions of the FCV capsid gene in individual cats ranged from 0.05 to 1.4% per week, with the highest rates generally being found in animals that either acquired the virus while in the shelter or were undergoing acute infection. These data suggest that despite the high prevalence and presence of multiple strains of FCV within the shelter, the spread of such pathogens may be restricted by various control measures, including good hygiene and biosecurity.

  8. 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

  9. Influence of laboratory animal hosts on the life cycle of Hyalomma marginatum and implications for an in vivo transmission model for Crimean-Congo hemorrhagic fever virus

    PubMed Central

    Gargili, Aysen; Thangamani, Saravanan; Bente, Dennis

    2013-01-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the most geographically widespread arboviruses and causes a severe hemorrhagic syndrome in humans. The virus circulates in nature in a vertebrate-tick cycle and ticks of the genus Hyalomma are the main vectors and reservoirs. Although the tick vector plays a central role in the maintenance and transmission of CCHFV in nature, comparatively little is known of CCHFV-tick interactions. This is mostly due to the fact that establishing tick colonies is laborious, and working with CCHFV requires a biosafety level 4 laboratory (BSL4) in many countries. Nonetheless, an in vivo transmission model is essential to understand the epidemiology of the transmission cycle of CCHFV. In addition, important parameters such as vectorial capacity of tick species, levels of infection in the host necessary to infect the tick, and aspects of virus transmission by tick bite including the influence of tick saliva, cannot be investigated any other way. Here, we evaluate the influence of different laboratory animal species as hosts supporting the life cycle of Hyalomma marginatum, a two-host tick. Rabbits were considered the host of choice for the maintenance of the uninfected colonies due to high larval attachment rates, shorter larval-nymphal feeding times, higher nymphal molting rates, high egg hatching rates, and higher conversion efficiency index (CEI). Furthermore, we describe the successful establishment of an in vivo transmission model for CCHFV in a BSL4 biocontainment setting using interferon knockout mice. This will give us a new tool to study the transmission and interaction of CCHFV with its tick vector. PMID:23971007

  10. Potential risk of viral transmission from flying foxes to domestic animals and humans on the southern coast of West Java, Indonesia.

    PubMed

    Basri, Chaerul; Arifin, Eko Muhammad Zainal; Takemae, Hitoshi; Hengjan, Yupadee; Iida, Keisuke; Sudarnika, Etih; Zahid, Abdul; Soejoedono, Retno Damayanti; Susetya, Heru; Sumiarto, Bambang; Kobayashi, Ryosuke; Agungpriyono, Srihadi; Hondo, Eiichi

    2017-07-20

    Flying foxes have been considered to be involved in the transmission of serious infectious diseases to humans. Using questionnaires, we aimed to determine the direct and/or indirect contacts of flying foxes in an Indonesian nature conservation area with domestic animals and humans living in the surrounding area. We surveyed 150 residents of 10 villages in West Java. Villages were classified into 3 groups: inside and/or within 1 km from the outer border of the conservation area and 1-5 km or 5-10 km away from the reserve's outer border. Data were collected by direct interview using a structured questionnaire consisting of the respondent characteristics (age, sex and occupation); histories of contacts between flying foxes and humans, dogs and other domestic animals; and knowledge about infectious diseases, mainly rabies, in flying foxes. We found that flying foxes from the nature conservation area often enter residential areas at night to look for food, especially during the fruit season. In these residential areas, flying foxes had direct contacts with humans and a few contacts with domestic animals, especially dogs. People who encounter flying foxes seldom used personal protective equipment, such as leather gloves, goggles and caps. The residents living around the conservation area mostly had poor knowledge about flying foxes and disease transmission. This situation shows that the population in this region is at a quite high risk for contracting infectious diseases from flying foxes.

  11. 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.

  12. Detection of pork and poultry meat and bone meals in animal feed using hyperspectral imaging

    USDA-ARS?s Scientific Manuscript database

    Animal feed with meat and bone meal (MBM) has been the source of bovine spongiform encephalopathy (BSE) in cattle and other livestock animals. Many countries have banned the use MBM as an animal feed ingredient. Spectral imaging techniques have shown potential for rapid assessment and authentication...

  13. Plasmodium yoelii nigeriensis (N67) Is a Robust Animal Model to Study Malaria Transmission by South American Anopheline Mosquitoes

    PubMed Central

    Molina-Cruz, Alvaro; Pimenta, Paulo F.; Barillas-Mury, Carolina

    2016-01-01

    Malaria is endemic in the American continent and the Amazonian rainforest is the region with the highest risk of transmission. However, the lack of suitable experimental models to infect malaria vectors from the Americas has limited the progress to understand the biology of transmission in this region. Anopheles aquasalis, a major vector in coastal areas of South America, was found to be highly refractory to infection with two strains of Plasmodium falciparum (NF54 and 7G8) and with Plasmodium berghei (mouse malaria), even when the microbiota was eliminated with antibiotics and oxidative stress was reduced with uric acid. In contrast, An. aquasalis females treated with antibiotics and uric acid are susceptible to infection with a second murine parasite, Plasmodium yoelii nigeriensis N67 (PyN67). Anopheles albimanus, one of the main malaria vectors in Central America, Southern Mexico and the Caribbean, was more susceptible to infection with PyN67 than An. aquasalis, even in the absence of any pre-treatment, but was still less susceptible than Anopheles stephensi. Disruption of the complement-like system in An. albimanus significantly enhanced PyN67 infection, indicating that the mosquito immune system is mounting effective antiplasmodial responses. PyN67 has the ability to infect a broad range of anophelines and is an excellent model to study malaria transmission by South American vectors. PMID:27911924

  14. Infectious titres of sheep scrapie and bovine spongiform encephalopathy agents cannot be accurately predicted from quantitative laboratory test results.

    PubMed

    González, Lorenzo; Thorne, Leigh; Jeffrey, Martin; Martin, Stuart; Spiropoulos, John; Beck, Katy E; Lockey, Richard W; Vickery, Christopher M; Holder, Thomas; Terry, Linda

    2012-11-01

    It is widely accepted that abnormal forms of the prion protein (PrP) are the best surrogate marker for the infectious agent of prion diseases and, in practice, the detection of such disease-associated (PrP(d)) and/or protease-resistant (PrP(res)) forms of PrP is the cornerstone of diagnosis and surveillance of the transmissible spongiform encephalopathies (TSEs). Nevertheless, some studies question the consistent association between infectivity and abnormal PrP detection. To address this discrepancy, 11 brain samples of sheep affected with natural scrapie or experimental bovine spongiform encephalopathy were selected on the basis of the magnitude and predominant types of PrP(d) accumulation, as shown by immunohistochemical (IHC) examination; contra-lateral hemi-brain samples were inoculated at three different dilutions into transgenic mice overexpressing ovine PrP and were also subjected to quantitative analysis by three biochemical tests (BCTs). Six samples gave 'low' infectious titres (10⁶·⁵ to 10⁶·⁷ LD₅₀ g⁻¹) and five gave 'high titres' (10⁸·¹ to ≥ 10⁸·⁷ LD₅₀ g⁻¹) and, with the exception of the Western blot analysis, those two groups tended to correspond with samples with lower PrP(d)/PrP(res) results by IHC/BCTs. However, no statistical association could be confirmed due to high individual sample variability. It is concluded that although detection of abnormal forms of PrP by laboratory methods remains useful to confirm TSE infection, infectivity titres cannot be predicted from quantitative test results, at least for the TSE sources and host PRNP genotypes used in this study. Furthermore, the near inverse correlation between infectious titres and Western blot results (high protease pre-treatment) argues for a dissociation between infectivity and PrP(res).

  15. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. 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

  17. 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

    Bargues, M Dolores; Artigas, Patricio; Khoubbane, Messaoud; Ortiz, Pedro; Naquira, Cesar; Mas-Coma, Santiago

    2012-08-15

    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. Therefore, ribosomal DNA ITS-2 and ITS-1, and mitochondrial DNA 16S and cox1 were sequenced by the dideoxy chain-termination method. 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. 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, given their transmission capacity

  18. 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. © 2012 Blackwell Verlag GmbH.

  19. Guinea Pig Prion Protein Supports Rapid Propagation of Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease Prions.

    PubMed

    Watts, Joel C; Giles, Kurt; Saltzberg, Daniel J; Dugger, Brittany N; Patel, Smita; Oehler, Abby; Bhardwaj, Sumita; Sali, Andrej; Prusiner, Stanley B

    2016-11-01

    The biochemical and neuropathological properties of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) prions are faithfully maintained upon transmission to guinea pigs. However, primary and secondary transmissions of BSE and vCJD in guinea pigs result in long incubation periods of ∼450 and ∼350 days, respectively. To determine if the incubation periods of BSE and vCJD prions could be shortened, we generated transgenic (Tg) mice expressing guinea pig prion protein (GPPrP). Inoculation of Tg(GPPrP) mice with BSE and vCJD prions resulted in mean incubation periods of 210 and 199 days, respectively, which shortened to 137 and 122 days upon serial transmission. In contrast, three different isolates of sporadic CJD prions failed to transmit disease to Tg(GPPrP) mice. Many of the strain-specified biochemical and neuropathological properties of BSE and vCJD prions, including the presence of type 2 protease-resistant PrP(Sc), were preserved upon propagation in Tg(GPPrP) mice. Structural modeling revealed that two residues near the N-terminal region of α-helix 1 in GPPrP might mediate its susceptibility to BSE and vCJD prions. Our results demonstrate that expression of GPPrP in Tg mice supports the rapid propagation of BSE and vCJD prions and suggest that Tg(GPPrP) mice may serve as a useful paradigm for bioassaying these prion isolates. Variant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE) prions are two of the prion strains most relevant to human health. However, propagating these strains in mice expressing human or bovine prion protein has been difficult because of prolonged incubation periods or inefficient transmission. Here, we show that transgenic mice expressing guinea pig prion protein are fully susceptible to vCJD and BSE prions but not to sporadic CJD prions. Our results suggest that the guinea pig prion protein is a better, more rapid substrate than either bovine or human prion protein for

  20. 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

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... carcass of BSE-positive cattle; (ii) The brains and spinal cords of cattle 30 months of age and older; (iii) The entire carcass of cattle not inspected and passed for human consumption as defined...

  1. 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

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... carcass of BSE-positive cattle; (ii) The brains and spinal cords of cattle 30 months of age and older; (iii) The entire carcass of cattle not inspected and passed for human consumption as defined...

  2. 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

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... carcass of BSE-positive cattle; (ii) The brains and spinal cords of cattle 30 months of age and older; (iii) The entire carcass of cattle not inspected and passed for human consumption as defined in...

  3. 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

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... carcass of BSE-positive cattle; (ii) The brains and spinal cords of cattle 30 months of age and older; (iii) The entire carcass of cattle not inspected and passed for human consumption as defined in...

  4. 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

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... carcass of BSE-positive cattle; (ii) The brains and spinal cords of cattle 30 months of age and older; (iii) The entire carcass of cattle not inspected and passed for human consumption as defined in...

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

    PubMed

    Sjaugi, Muhammad Farhan; Tan, Swan; Abd Raman, Hadia Syahirah; Lim, Wan Ching; Nik Mohamed, Nik Elena; August, J; Khan, Asif M

    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.

  6. 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

  7. 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

  8. Genetic analysis of the Gdh and Bg genes of animal-derived Giardia duodenalis isolates in Northeastern China and evaluation of zoonotic transmission potential.

    PubMed

    Liu, Aiqin; Yang, Fengkun; Shen, Yujuan; Zhang, Weizhe; Wang, Rongjun; Zhao, Wei; Zhang, Longxian; Ling, Hong; Cao, Jianping

    2014-01-01

    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. 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. 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.

  9. 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

  10. 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.

  11. Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform Encephalopathy

    PubMed Central

    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 PrPres 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

  12. Phylogenetic analysis of 626 hepatitis E virus (HEV) isolates from humans and animals in China (1986-2011) showing genotype diversity and zoonotic transmission.

    PubMed

    Liu, Peng; Li, Lingjun; Wang, Ling; Bu, Qiuning; Fu, Hongwei; Han, Jian; Zhu, Yonghong; Lu, Fengmin; Zhuang, Hui

    2012-03-01

    Hepatitis E is considered as a public health problem in China. To determine the overall molecular epidemiology of hepatitis E virus (HEV) and analyze the situation of cross-species transmission between humans and swine in China over the last 25 years (1986-2011), 626 HEV complete and partial sequences (89 isolates identified by our group) isolated from humans and animals in China were retrieved from GenBank and subjected to phylogenetic analysis. There were three genotypes and 11 sub-genotypes of HEV prevailing in China. Furthermore, rabbit HEVs, of which the genotype is controversial, are also widespread in China. Genotype 1 was the most isolated genotype prior to 2000 and mainly detected in Xinjiang, Beijing and East China. However, genotype 4, which was identified in most regions of China during the last 10 years, has overtaken genotype 1 in frequency of isolation nationwide. Genotype 3 HEV strains have been found only in eastern China and were thought to be imported from Japan. Both genotypes 3 and 4 were found in humans and swine and cross-species transmission from pigs to humans of the two genotypes may have occurred in Northeast, Northwest, North, East and South China. These results indicate that HEV strains with considerable genetic diversity are widespread and the zoonotic transmission between swine and humans appears ubiquitous in China.

  13. 9 CFR 94.18 - Restrictions on importation of meat and edible products from ruminants due to bovine spongiform...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... and edible products from ruminants due to bovine spongiform encephalopathy. 94.18 Section 94.18... importation of meat and edible products from ruminants due to bovine spongiform encephalopathy. (a)(1) Bovine... as provided in paragraph (c) of this section, milk, and milk products) from ruminants that have...

  14. 9 CFR 94.18 - Restrictions on importation of meat and edible products from ruminants due to bovine spongiform...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... and edible products from ruminants due to bovine spongiform encephalopathy. 94.18 Section 94.18... importation of meat and edible products from ruminants due to bovine spongiform encephalopathy. (a)(1) Bovine... as provided in paragraph (c) of this section, milk, and milk products) from ruminants that have...

  15. 9 CFR 94.18 - Restrictions on importation of meat and edible products from ruminants due to bovine spongiform...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... and edible products from ruminants due to bovine spongiform encephalopathy. 94.18 Section 94.18... importation of meat and edible products from ruminants due to bovine spongiform encephalopathy. (a)(1) Bovine... as provided in paragraph (c) of this section, milk, and milk products) from ruminants that have...

  16. 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

    ... and edible products from ruminants due to bovine spongiform encephalopathy. 94.18 Section 94.18... § 94.18 Restrictions on importation of meat and edible products from ruminants due to bovine spongiform... ruminants that have been in any of the regions listed in paragraph (a) of this section is prohibited....

  17. 9 CFR 94.18 - Restrictions on importation of meat and edible products from ruminants due to bovine spongiform...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and edible products from ruminants due to bovine spongiform encephalopathy. 94.18 Section 94.18... importation of meat and edible products from ruminants due to bovine spongiform encephalopathy. (a)(1) Bovine... as provided in paragraph (c) of this section, milk, and milk products) from ruminants that have...

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

    PubMed

    Gavier-Widén, Dolores; Nöremark, Maria; Langeveld, Jan P M; Stack, Mick; Biacabe, Anne-Gaëlle; Vulin, Johann; Chaplin, Melanie; Richt, Jürgen A; Jacobs, Jorg; Acín, Cristina; Monleón, Eva; Renström, Lena; Klingeborn, Berndt; Baron, Thierry G M

    2008-01-01

    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, because several molecular features of the protease-resistant prion protein (PrP(res)) were different from classical BSE. The differences included higher susceptibility for proteinase K, higher molecular weight of the PrP(res) bands, affinity to the N-terminus-specific antibodies 12B2 and P4, and peculiar banding pattern with antibody SAF84 showing an additional band at the 14 kDa position. The molecular characteristics were in accordance to previous descriptions of H-type BSE. This report shows that a range of Western blot techniques and antibodies can be applied to confirm H-type BSE and further describes that the ratio of the amounts of PrPres#1 and PrPres#2, after deglycosylation, depends on the antibody used during processing. Immunohistochemistry on sections of medulla at the level of the obex applying antibodies with epitopes covering a broad range of the PrP sequence showed accumulation of disease-specific PrP (PrP(d)) in the gray matter. Fine punctate deposition in the neuropil was the most predominant type and was more severe in BSE target nuclei. The types of PrP(d) deposition are described in comparison with classical BSE. PrP-gene sequencing showed 6 copy octarepeat alleles and no abnormalities. It is postulated that the disease had a spontaneous origin, rather than having had been acquired in the BSE epidemic.

  19. In vivo transmission and dynamics of deleted genomes after experimental infection of woodchuck hepatitis B virus in adult animals.

    PubMed

    La Sorsa, Valentina; Argentini, Claudio; Bruni, Roberto; Villano, Umberta; Giuseppetti, Roberto; Rapicetta, Maria

    2002-10-01

    The presence of Deleted Genomes has been shown in a number of viral models including Hepadnaviridae. The analysis of woodchuck hepatitis B virus (WHV) population after experimental infection of woodchuck 197 (W197) with WHV7-PI inoculum revealed the presence of two Deleted Genomes: DG600 lacking a 1330 bp region (Core/Polymerase/PreS1) and DG900 showing a deletion of 869 nts (Pol/PreS/S). These mutants were also present in WHV7-PI. The successive WHV experimental infections in adult animals were performed using W197-w7 inoculum containing DG600 and DG900. Infections were divided into three groups presenting different patterns of viral replication, different presence of markers, occurrence of variants and persistence of infection. The first group displayed 2-3 weeks viremic phase and WHV-DNA titres of 10-30 ng/ml; the second a longer viremic phase (8-9 weeks) and higher WHV-DNA titres (up to 78 ng/ml). In contrast, the third group exhibited lifetime presence of WHV-DNA and WHVeAg in serum and viral replication in liver. The Deleted Genomes were transmitted in the newly infected animals with the same genomic organization. DG600 was persistently found only in chronically infected woodchuck, whereas a different pattern of presence was described for DG900. The characterization of these classes of deleted mutants in woodchuck-WHV model raises new questions on the link between DGs and persistent infections.

  20. MEAT AND BONE MEAL AND MINERAL FEED ADDITIVES MAY INCREASE THE RISK OF ORAL PRION DISEASE TRANSMISSION

    PubMed Central

    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. PMID:21218345

  1. 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.

  2. 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.

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

    PubMed

    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.

  4. Neuronal degeneration in the gerbil brainstem is associated with spongiform lesions.

    PubMed

    McGinn, M D; Faddis, B T

    1998-05-01

    Spongiform lesions arise in dendrites and glia in the brainstem of domestic Mongolian gerbils. Most pronounced within the cochlear nucleus (CN), this disorder is dynamic and progressive; the lesions increase in number, size, and extent with age. It has not been clear whether these spongioid lesions either cause or are associated with significant neural degeneration. In contrast, feral Mongolian gerbils (wild-trapped in Tuva) and their offspring show few spongiform lesions. The Tuvan gerbils provide an appropriate within-species control. We compared degeneration in the brainstem of domestic and Tuvan gerbils using the amino-cupric-silver (ACS) stain of de Olmos et al. [(1994) Neurotoxicol. Teratol., 16:545-561]. Positive histologic controls were provided by cerebellar stab wounds in domestic gerbils and by unilateral kainic acid injections into the CN of Tuvan gerbils. The ACS stain revealed extensive degeneration of axons, terminals, dendrites, and neurons in the brainstem of domestic gerbils. Neurodegeneration was most pronounced in the CN and was coextensive with spongiform lesions. Neurodegeneration was also seen in the trapezoid body, lateral lemniscus, and inferior colliculus, but was less pronounced than in the CN. The cerebellar stab wounds resulted in silver-stained Purkinje cells restricted to the stab wound local region. Kainic acid produced extensive neuronal and spongiform degeneration of the injected CN that was very similar to that spontaneously occurring in domestic gerbils. In contrast, the non-injected CN of Tuvan gerbils showed no neuronal or spongiform degeneration with the ACS stain. We conclude that, in domestic gerbils, the naturally occurring spongiform lesions of the CN and the accompanying neurodegeneration are both results of a common mechanism, most probably excitotoxic.

  5. 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

  6. Protective Effect of Val129-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease

    PubMed Central

    Fernández-Borges, Natalia; Espinosa, Juan Carlos; Marín-Moreno, Alba; Aguilar-Calvo, Patricia; Asante, Emmanuel A.; Kitamoto, Tetsuyuki; Mohri, Shirou; Andréoletti, Olivier

    2017-01-01

    Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met129) or valine (Val129) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met129 homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Here, we found that transgenic mice homozygous for Val129 Hu-PrP show severely restricted propagation of the BSE prion strain, but this constraint can be partially overcome by adaptation of the BSE agent to the Met129 Hu-PrP. In addition, the transmission of vCJD to transgenic mice homozygous for Val129 Hu-PrP resulted in a prion with distinct strain features. These observations may indicate increased risk for vCJD secondary transmission in Val129 Hu-PrP–positive humans with the emergence of new strain features. PMID:28820136

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

    USDA-ARS?s Scientific Manuscript database

    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...

  8. 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.

  9. Animal models of bovine leukemia virus and human T-lymphotrophic virus type-1: insights in transmission and pathogenesis.

    PubMed

    Lairmore, Michael D

    2014-02-01

    Bovine leukemia virus (BLV) and human T-lymphotrophic virus type-1 (HTLV-1) are related retroviruses associated with persistent and lifelong infections and a low incidence of lymphomas within their hosts. Both viruses can be spread through contact with bodily fluids containing infected cells, most often from mother to offspring through breast milk. Each of these complex retroviruses contains typical gag, pol, and env genes but also unique, nonstructural proteins encoded from the pX region. These nonstructural genes encode the Tax and Rex regulatory proteins, as well as novel proteins essential for viral spread in vivo. Improvements in the molecular tools to test these viral determinants in cellular and animal models have provided new insights into the pathogenesis of each virus. Comparisons of BLV and HTLV-1 provide insights into mechanisms of spread and tumor formation, as well as potential approaches to therapeutic intervention against the infections.

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

    PubMed Central

    Perrott, Matthew R.; Sigurdson, Christina J.; Mason, Gary L.

    2013-01-01

    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 (PrPCWD) amplification in lymphoid tissues, neural invasion and florid transmissible spongiform encephalopathy lesions resembling those in native cervid hosts. The ferrets developed extensive PrPCWD accumulation in the nervous system, retina and olfactory epithelium, with lesser deposition in tongue, muscle, salivary gland and the vomeronasal organ. PrPCWD 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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  12. Detergents modify proteinase K resistance of PrPSc in different transmissible spongiform encephalopathies (TSEs)

    PubMed Central

    Breyer, Johanna; Wemheuer, Wiebke M.; Wrede, Arne; Graham, Catherine; Benestad, Sylvie L.; Brenig, Bertram; Richt, Jürgen A.; Schulz-Schaeffer, Walter J.

    2012-01-01

    Prion diseases are diagnosed by the detection of their proteinase K-resistant prion protein fragment (PrPSc). Various biochemical protocols use different detergents for the tissue preparation. We found that the resistance of PrPSc against proteinase K may vary strongly with the detergent used. In our study, we investigated the influence of the most commonly used detergents on eight different TSE agents derived from different species and distinct prion disease forms. For a high throughput we used a membrane adsorbtion assay to detect small amounts of prion aggregates, as well as Western blotting. Tissue lysates were prepared using DOC, SLS, SDS or Triton X-100 in different concentrations and these were digested with various amounts of proteinase K. Detergents are able to enhance or diminish the detectability of PrPSc after proteinase K digestion. Depending on the kind of detergent, its concentration - but also on the host species that developed the TSE and the disease form or prion type - the detectability of PrPSc can be very different. The results obtained here may be helpful during the development or improvement of a PrPSc detection method and they point towards a detergent effect that can be additionally used for decontamination purposes. A plausible explanation for the detergent effects described in this article could be an interaction with the lipids associated with PrPSc that may stabilize the aggregates. PMID:22226540

  13. Detergents modify proteinase K resistance of PrP Sc in different transmissible spongiform encephalopathies (TSEs).

    PubMed

    Breyer, Johanna; Wemheuer, Wiebke M; Wrede, Arne; Graham, Catherine; Benestad, Sylvie L; Brenig, Bertram; Richt, Jürgen A; Schulz-Schaeffer, Walter J

    2012-05-25

    Prion diseases are diagnosed by the detection of their proteinase K-resistant prion protein fragment (PrP(Sc)). Various biochemical protocols use different detergents for the tissue preparation. We found that the resistance of PrP(Sc) against proteinase K may vary strongly with the detergent used. In our study, we investigated the influence of the most commonly used detergents on eight different TSE agents derived from different species and distinct prion disease forms. For a high throughput we used a membrane adsorption assay to detect small amounts of prion aggregates, as well as Western blotting. Tissue lysates were prepared using DOC, SLS, SDS or Triton X-100 in different concentrations and these were digested with various amounts of proteinase K. Detergents are able to enhance or diminish the detectability of PrP(Sc) after proteinase K digestion. Depending on the kind of detergent, its concentration - but also on the host species that developed the TSE and the disease form or prion type - the detectability of PrP(Sc) can be very different. The results obtained here may be helpful during the development or improvement of a PrP(Sc) detection method and they point towards a detergent effect that can be additionally used for decontamination purposes. A plausible explanation for the detergent effects described in this article could be an interaction with the lipids associated with PrP(Sc) that may stabilize the aggregates. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. T cells infiltrate the brain in murine and human transmissible spongiform encephalopathies.

    PubMed

    Lewicki, Hanna; Tishon, Antoinette; Homann, Dirk; Mazarguil, Honoré; Laval, Françoise; Asensio, Valerie C; Campbell, Iain L; DeArmond, Stephen; Coon, Bryan; Teng, Chao; Gairin, Jean Edouard; Oldstone, Michael B A

    2003-03-01

    CD4 and CD8 T lymphocytes infiltrate the parenchyma of mouse brains several weeks after intracerebral, intraperitoneal, or oral inoculation with the Chandler strain of mouse scrapie, a pattern not seen with inoculation of prion protein knockout (PrP(-/-)) mice. Associated with this cellular infiltration are expression of MHC class I and II molecules and elevation in levels of the T-cell chemokines, especially macrophage inflammatory protein 1beta, IFN-gamma-inducible protein 10, and RANTES. T cells were also found in the central nervous system (CNS) in five of six patients with Creutzfeldt-Jakob disease. T cells harvested from brains and spleens of scrapie-infected mice were analyzed using a newly identified mouse PrP (mPrP) peptide bearing the canonical binding motifs to major histocompatibility complex (MHC) class I H-2(b) or H-2(d) molecules, appropriate MHC class I tetramers made to include these peptides, and CD4 and CD8 T cells stimulated with 15-mer overlapping peptides covering the whole mPrP. Minimal to modest K(b) tetramer binding of mPrP amino acids (aa) 2 to 9, aa 152 to 160, and aa 232 to 241 was observed, but such tetramer-binding lymphocytes as well as CD4 and CD8 lymphocytes incubated with the full repertoire of mPrP peptides failed to synthesize intracellular gamma interferon (IFN-gamma) or tumor necrosis factor alpha (TNF-alpha) cytokines and were unable to lyse PrP(-/-) embryo fibroblasts or macrophages coated with (51)Cr-labeled mPrP peptide. These results suggest that the expression of PrP(sc) in the CNS is associated with release of chemokines and, as shown previously, cytokines that attract and retain PrP-activated T cells and, quite likely, bystander activated T cells that have migrated from the periphery into the CNS. However, these CD4 and CD8 T cells are defective in such an effector function(s) as IFN-gamma and TNF-alpha expression or release or lytic activity.

  15. T Cells Infiltrate the Brain in Murine and Human Transmissible Spongiform Encephalopathies†

    PubMed Central

    Lewicki, Hanna; Tishon, Antoinette; Homann, Dirk; Mazarguil, Honoré; Laval, Françoise; Asensio, Valerie C.; Campbell, Iain L.; DeArmond, Stephen; Coon, Bryan; Teng, Chao; Gairin, Jean Edouard; Oldstone, Michael B. A.

    2003-01-01

    CD4 and CD8 T lymphocytes infiltrate the parenchyma of mouse brains several weeks after intracerebral, intraperitoneal, or oral inoculation with the Chandler strain of mouse scrapie, a pattern not seen with inoculation of prion protein knockout (PrP−/−) mice. Associated with this cellular infiltration are expression of MHC class I and II molecules and elevation in levels of the T-cell chemokines, especially macrophage inflammatory protein 1β, IFN-γ-inducible protein 10, and RANTES. T cells were also found in the central nervous system (CNS) in five of six patients with Creutzfeldt-Jakob disease. T cells harvested from brains and spleens of scrapie-infected mice were analyzed using a newly identified mouse PrP (mPrP) peptide bearing the canonical binding motifs to major histocompatibility complex (MHC) class I H-2b or H-2d molecules, appropriate MHC class I tetramers made to include these peptides, and CD4 and CD8 T cells stimulated with 15-mer overlapping peptides covering the whole mPrP. Minimal to modest Kb tetramer binding of mPrP amino acids (aa) 2 to 9, aa 152 to 160, and aa 232 to 241 was observed, but such tetramer-binding lymphocytes as well as CD4 and CD8 lymphocytes incubated with the full repertoire of mPrP peptides failed to synthesize intracellular gamma interferon (IFN-γ) or tumor necrosis factor alpha (TNF-α) cytokines and were unable to lyse PrP−/− embryo fibroblasts or macrophages coated with 51Cr-labeled mPrP peptide. These results suggest that the expression of PrPsc in the CNS is associated with release of chemokines and, as shown previously, cytokines that attract and retain PrP-activated T cells and, quite likely, bystander activated T cells that have migrated from the periphery into the CNS. However, these CD4 and CD8 T cells are defective in such an effector function(s) as IFN-γ and TNF-α expression or release or lytic activity. PMID:12610154

  16. The impact of diseases on the importation of animals and animal products.

    PubMed

    Walton, T E

    2000-01-01

    For decades the veterinary services of the United States and other nations protected their livestock and poultry industries from the ravages of introduced animal diseases by rigorous import restrictions. This policy of zero risk frequently translated to no or reduced trade in animals and animal products or dramatic trade inequities. However, GATT articles enforced by the WTO require that imported products be treated no less favorably than domestically produced goods with regard to animal health restrictions. Under authority from the WTO, the OIE establishes recommendations and guidelines for the regulation of trade in animals and products of animal origin through the OIE International Animal Health Code, sets animal health standards, and reports global animal health situations and statuses. Diseases often have a dramatic impact on the animal agricultural industries of a nation--disease outbreaks may be deleterious to the competitiveness of the products of one nation but offer opportunities for others. The potential dangers of lax vigilance, insufficient scientifically valid data, inadequate SPS measures, and errors in assessing risk can turn the heady experience of seemingly unlimited growth in international markets and demand for one's products into a catastrophic return to reality. The experience of the United Kingdom and countries of Europe with bovine spongiform encephalopathy is a case in point. It is estimated that the cost of the outbreak of this disease to the economy of the UK has been more than $3 billion. Responses of their trading partners, including the US, to this outbreak were abrupt and restrictive. Although the decision was controversial, the US stopped importation of live cattle from the UK in the late 1980's and subsequently, in 1997, importation of all products of ruminant origin was stopped from all countries of Europe. The transmission of the disease to continental Europe and the disclosure that the pathogen was associated with a fatal human

  17. Detection of bovine central nervous system tissues in rendered animal by-products by one-step real-time reverse transcription PCR assay.

    PubMed

    Andrievskaia, Olga; Tangorra, Erin

    2014-12-01

    Contamination of rendered animal byproducts with central nervous system tissues (CNST) from animals with bovine spongiform encephalopathy is considered one of the vehicles of disease transmission. Removal from the animal feed chain of CNST originated from cattle of a specified age category, species-labeling of rendered meat products, and testing of rendered products for bovine CNST are tasks associated with the epidemiological control of bovine spongiform encephalopathy. A single-step TaqMan real-time reverse transcriptase (RRT) PCR assay was developed and evaluated for specific detection of bovine glial fibrillary acidic protein (GFAP) mRNA, a biomarker of bovine CNST, in rendered animal by-products. An internal amplification control, mammalian b -actin mRNA, was coamplified in the duplex RRT-PCR assay to monitor amplification efficiency, normalize amplification signals, and avoid false-negative results. The functionality of the GFAP mRNA RRT-PCR was assessed through analysis of laboratory-generated binary mixtures of bovine central nervous system (CNS) and muscle tissues treated under various thermal settings imitating industrial conditions. The assay was able to detect as low as 0.05 % (wt/wt) bovine brain tissue in binary mixtures heat treated at 110 to 130°C for 20 to 60 min. Further evaluation of the GFAP mRNA RRT-PCR assay involved samples of industrial rendered products of various species origin and composition obtained from commercial sources and rendering plants. Low amounts of bovine GFAP mRNA were detected in several bovine-rendered products, which was in agreement with declared species composition. An accurate estimation of CNS tissue content in industrial-rendered products was complicated due to a wide range of temperature and time settings in rendering protocols. Nevertheless, the GFAP mRNA RRT-PCR assay may be considered for bovine CNS tissue detection in rendered products in combination with other available tools (for example, animal age

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

    USDA-ARS?s Scientific Manuscript database

    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...

  19. Bovine Spongiform Encephalopathy (BSE), or Mad Cow Disease

    MedlinePlus

    ... on this page will be unavailable. For more information about this message, please visit this page: About ... of the transmissible agent is not well understood. Currently, the most accepted theory is that the agent is a modified form ...

  20. Influence of Co-57 and CT Transmission Measurements on the Quantification Accuracy and Partial Volume Effect of a Small Animal PET Scanner.

    PubMed

    Mannheim, Julia G; Schmid, Andreas M; Pichler, Bernd J

    2017-03-30

    Non-invasive in vivo positron emission tomography (PET) provides high detection sensitivity in the nano- to picomolar range and in addition to other advantages, the possibility to absolutely quantify the acquired data. The present study focuses on the comparison of transmission data acquired with an X-ray computed tomography (CT) scanner or a Co-57 source for the Inveon small animal PET scanner (Siemens Healthcare, Knoxville, TN, USA), as well as determines their influences on the quantification accuracy and partial volume effect (PVE). A special focus included the impact of the performed calibration on the quantification accuracy. Phantom measurements were carried out to determine the quantification accuracy, the influence of the object size on the quantification, and the PVE for different sphere sizes, along the field of view and for different contrast ratios. An influence of the emission activity on the Co-57 transmission measurements was discovered (deviations up to 24.06 % measured to true activity), whereas no influence of the emission activity on the CT attenuation correction was identified (deviations <3 % for measured to true activity). The quantification accuracy was substantially influenced by the applied calibration factor and by the object size. The PVE demonstrated a dependency on the sphere size, the position within the field of view, the reconstruction and correction algorithms and the count statistics. Depending on the reconstruction algorithm, only ∼30-40 % of the true activity within a small sphere could be resolved. The iterative 3D reconstruction algorithms uncovered substantially increased recovery values compared to the analytical and 2D iterative reconstruction algorithms (up to 70.46 % and 80.82 % recovery for the smallest and largest sphere using iterative 3D reconstruction algorithms). The transmission measurement (CT or Co-57 source) to correct for attenuation did not severely influence the PVE. The analysis of the quantification

  1. Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle.

    PubMed

    Wells, G A H; Konold, T; Arnold, M E; Austin, A R; Hawkins, S A C; Stack, M; Simmons, M M; Lee, Y H; Gavier-Widén, D; Dawson, M; Wilesmith, J W

    2007-04-01

    The dose-response of cattle exposed to the bovine spongiform encephalopathy (BSE) agent is an important component of modelling exposure risks for animals and humans and thereby, the modulation of surveillance and control strategies for BSE. In two experiments calves were dosed orally with a range of amounts of a pool of brainstems from BSE-affected cattle. Infectivity in the pool was determined by end-point titration in mice. Recipient cattle were monitored for clinical disease and, from the incidence of pathologically confirmed cases and their incubation periods (IPs), the attack rate and IP distribution according to dose were estimated. The dose at which 50 % of cattle would be clinically affected was estimated at 0.20 g brain material used in the experiment, with 95 % confidence intervals of 0.04-1.00 g. The IP was highly variable across all dose groups and followed a log-normal distribution, with decreasing mean as dose increased. There was no evidence of a threshold dose at which the probability of infection became vanishingly small, with 1/15 (7 %) of animals affected at the lowest dose (1 mg).

  2. Enhanced virulence of sheep-passaged bovine spongiform encephalopathy agent is revealed by decreased polymorphism barriers in prion protein conversion studies.

    PubMed

    Priem, Jan; Langeveld, Jan P M; van Keulen, Lucien J M; van Zijderveld, Fred G; Andreoletti, Olivier; Bossers, Alex

    2014-03-01

    Bovine spongiform encephalopathy (BSE) can be efficiently transmitted to small ruminants (sheep and goats) with certain prion protein (PrP) genotypes. Polymorphisms in PrP of both the host and donor influence the transmission efficiency of transmissible spongiform encephalopathies (TSEs) in general. These polymorphisms in PrP also modulate the PrP conversion underlying TSE agent replication. Here we demonstrate that single-round protein misfolding cyclic amplification (PMCA) can be used to assess species and polymorphism barriers at the molecular level. We assessed those within and between the ovine and bovine species in vitro using a variety of natural scrapie and experimentally generated cross-species BSE agents. These BSE agents include ovBSE-ARQ isolates (BSE derived from sheep having the ARQ/ARQ PrP genotype), and two unique BSE-derived variants: BSE passaged in VRQ/VRQ sheep and a cow BSE agent isolate generated by back-transmission of ovBSE-ARQ into its original host. PMCA allowed us to quantitatively determine PrP conversion profiles that correlated with known in vivo transmissibility and susceptibility in the two ruminant species in which strain-specific molecular signatures, like its molecular weight after protease digestion, were maintained. Furthermore, both BSE agent isolates from ARQ and VRQ sheep demonstrated a surprising transmission profile in which efficient transmissions to both sheep and bovine variants was combined. Finally, all data support the notion that ARQ-derived sheep BSE points to a significant increase in virulence compared to all other tested scrapie- and BSE-derived variants reflected by the increased conversion efficiencies of previously inefficient convertible PrP variants (including the so-called "resistant" sheep ARR variant). Prion diseases such as scrapie in sheep and goats, BSE in cattle, and Creutzfeldt-Jakob disease (CJD) in humans are fatal neurodegenerative diseases caused by prions. BSE is known to be transmissible to a

  3. Enhanced Virulence of Sheep-Passaged Bovine Spongiform Encephalopathy Agent Is Revealed by Decreased Polymorphism Barriers in Prion Protein Conversion Studies

    PubMed Central

    Priem, Jan; Langeveld, Jan P. M.; van Keulen, Lucien J. M.; van Zijderveld, Fred G.; Andreoletti, Olivier

    2014-01-01

    ABSTRACT Bovine spongiform encephalopathy (BSE) can be efficiently transmitted to small ruminants (sheep and goats) with certain prion protein (PrP) genotypes. Polymorphisms in PrP of both the host and donor influence the transmission efficiency of transmissible spongiform encephalopathies (TSEs) in general. These polymorphisms in PrP also modulate the PrP conversion underlying TSE agent replication. Here we demonstrate that single-round protein misfolding cyclic amplification (PMCA) can be used to assess species and polymorphism barriers at the molecular level. We assessed those within and between the ovine and bovine species in vitro using a variety of natural scrapie and experimentally generated cross-species BSE agents. These BSE agents include ovBSE-ARQ isolates (BSE derived from sheep having the ARQ/ARQ PrP genotype), and two unique BSE-derived variants: BSE passaged in VRQ/VRQ sheep and a cow BSE agent isolate generated by back-transmission of ovBSE-ARQ into its original host. PMCA allowed us to quantitatively determine PrP conversion profiles that correlated with known in vivo transmissibility and susceptibility in the two ruminant species in which strain-specific molecular signatures, like its molecular weight after protease digestion, were maintained. Furthermore, both BSE agent isolates from ARQ and VRQ sheep demonstrated a surprising transmission profile in which efficient transmissions to both sheep and bovine variants was combined. Finally, all data support the notion that ARQ-derived sheep BSE points to a significant increase in virulence compared to all other tested scrapie- and BSE-derived variants reflected by the increased conversion efficiencies of previously inefficient convertible PrP variants (including the so-called “resistant” sheep ARR variant). IMPORTANCE Prion diseases such as scrapie in sheep and goats, BSE in cattle, and Creutzfeldt-Jakob disease (CJD) in humans are fatal neurodegenerative diseases caused by prions. BSE is known to

  4. 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

  5. Detection and Discrimination of Classical and Atypical L-Type Bovine Spongiform Encephalopathy by Real-Time Quaking-Induced Conversion

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

    Piccardo, Pedro; Cervenak, Juraj; Bu, Ming; Miller, Lindsay; Asher, David M

    2014-07-01

    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 (PrP(TSE)), 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 PrP(TSE) 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.

  7. 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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. The basic reality of mind and spongiform diseases.

    PubMed

    Axelsson, S

    2001-11-01

    A change in handedness (chirality) in some amino acids appears to be the basic physical change in degradation-resistant proteins (prions) found in conditions such as Creutzfeldt-Jacob disease (CJD), Alzheimer's disease (AD), bovine spongiform encephalopathy (BSE) and ovine scrapie. The affected structures are primarily innervated by cholinergic nerves. Much evidence suggests that these so-called prions (here named chirons) are harmless, non-infectious products. The importance of the cholinergic system allows a new simplified interpretation of these conditions. The main steps are the acetylcholine-cholinesterase splitting of body water with release of free protons in solution, followed by electron dissipation, dioxygen activation and Ca-fluxes. Abiotic physics conserves parity and symmetry by equal amounts of L- and D-forms of molecules. In contrast, the asymmetric pattern of life must be homochiral. Such biomolecules dissolve in water and are thus able to interact in cholinergic hydrodynamics. It is supposed that the instability of the composite weak force by beta-decay causes changes in chirality. These extremely rare events are not frequent enough to explain disease pathology. Experimental, accidental, surgical and abusive inoculations will propagate chirons according to the physical law of self-replication, which also occurs in test tubes without added biological products. Chirons will not be degraded into amino acids in the alimentary canal and will, because they are indigestible, leave the body with the faeces. Chirons are inert also to the immune system and will be engulfed without reaction by phagocytosing cells. They are then stored away in tissues, where they do no harm (if not detected and suspected to be deleterious, thereby causing pathogenic anxiety). The cholinergic system reacts to all kinds of integrity threats and it is this reaction which I propose causes the so-called prion diseases. This pathology seems generally valid, and is here exemplified

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

    USDA-ARS?s Scientific Manuscript database

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  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. Assessing the time taken for a surveillance system to detect a re-emergence of bovine spongiform encephalopathy in cattle.

    PubMed

    Simons, Robin R L; Arnold, Mark E; Adkin, Amie

    2017-03-01

    During the bovine spongiform encephalopathy (BSE) epidemic in July 2001 the European Commission established a surveillance scheme for the comprehensive sampling of all BSE clinical suspects, healthy slaughter (HS) animals >30months, and all emergency slaughter and fallen stock animals tested when >24months. With the exponential decline in classical BSE cases, this comprehensive surveillance system has been successively modified to become risk-based, targeting those exit streams and ages where cases from the original epidemic are most likely to be detected. Such reductions in testing are not without losses in the information subsequently collected, which could affect the sensitivity of the surveillance system to relatively small changes in the underlying prevalence of BSE across the European Union (EU). Here we report on a cohort-based approach to estimate the time taken for EU surveillance to observe a theoretical re-emergence of BSE in cattle. A number of surveillance schemes were compared. The baseline scheme considered detection being triggered by at least one case in the 'age window' 48-72 months in the fallen stock or emergency slaughter exit streams. Alternative schemes changed the start and end of this age window as well as considering testing for HS cattle. Under the baseline scheme, an estimated 15 years would lapse ([2.5th, 97.5th] percentiles=[10,24]) prior to detection, during which time 2867 infected animals ([2.5th, 97.5th]=[1722,6967]) would enter the slaughter population. These animals would be predominantly young animals (majority <24months) showing no clinical signs. This baseline scheme reduced the time to detection by 2 years, compared to a scheme where only clinical suspects were tested assuming BSE symptoms are recognised to the same degree by veterinary surgeons. Additional testing of younger animals did not improve detection as young infected animals were unlikely to test positive, but testing of older animals reduced the time to detection

  15. Transcriptome analysis of the medulla tissue from cattle in response to bovine spongiform encephalopathy using digital gene expression tag profiling.

    PubMed

    Basu, Urmila; Almeida, Luciane; Olson, N Eric; Meng, Yan; Williams, John L; Moore, Stephen S; Guan, Le Luo

    2011-01-01

    Bovine spongiform encephalopathy (BSE) is a transmissible, fatal neurodegenerative disorder of cattle produced by prions. The use of excessive parallel sequencing for comparison of gene expression in bovine control and infected tissues may help to elucidate the molecular mechanisms associated with this disease. In this study, tag profiling Solexa sequencing was used for transcriptome analysis of bovine brain tissues. Replicate libraries were prepared from mRNA isolated from control and infected (challenged with 100 g of BSE-infected brain) medulla tissues 45 mo after infection. For each library, 5-6 million sequence reads were generated and approximately 67-70% of the reads were mapped against the Bovine Genome database to approximately 13,700-14,120 transcripts (each having at least one read). About 42-47% of the total reads mapped uniquely. Using the GeneSifter software package, 190 differentially expressed (DE) genes were identified (>2.0-fold change, p < .01): 73 upregulated and 117 downregulated. Seventy-nine DE genes had functions described in the Gene Ontology (GO) database and 16 DE genes were involved in 38 different pathways described in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Digital analysis expression by tag profiling may be a powerful approach to comprehensive transcriptome analysis to identify changes associated with disease progression, leading to a better understanding of the underlying mechanism of pathogenesis of BSE.

  16. Potential risk of zoonotic transmission from young swine to human: seroepidemiological and genetic characterization of hepatitis E virus in human and various animals in Beijing, China.

    PubMed

    Geng, J; Wang, L; Wang, X; Fu, H; Bu, Q; Liu, P; Zhu, Y; Wang, M; Sui, Y; Zhuang, H

    2011-10-01

    The aim of this study was to further investigate the prevalence of infection and genotype of hepatitis E virus (HEV) among different species of animals, people whose works are related to pigs and the general population in the suburb of Beijing, China. Serum and faecal samples were collected from 10 animal species and humans. Anti-HEV was detected by enzyme immunoassays (EIA); HEV RNA was amplified by reverse transcription-nested polymerase chain reaction (RT-nPCR) method. PCR products were cloned and sequenced. The isolated swine HEV sequences were analysed phylogenetically. The positive rates of serum anti-HEV in swine, cattle, milk cow, horse, sheep, donkey, dog, duck, chicken, pig farm workers and slaughterhouse workers, and general population were 81.17% (802/988), 25.29% (66/261), 14.87% (40/269), 14.29% (40/280), 9.30% (53/514), 0 (0/25), 0 (0/20), 2.53% (8/316), 3.03% (7/231), 58.73% (37/63), 35.87% (66/184) and 20.06% (538/2682), respectively. The anti-HEV prevalence in adult swine (≥ 6 months) and younger swine (≤ 3 months) was 91.49% (591/646) and 61.7% (211/342), respectively. The positive rate of HEV RNA in young swine faeces was 47.94% (93/194). All 93 isolates from the younger swine shared 87.8-100% nucleotide homology with each other and had identities of 75.6-78.9%, 73.9-76.1%, 76.4-80.6% and 83.1-95.0% with the corresponding regions of genotypes 1-4 HEV, respectively. Phylogenetic analysis showed that all HEV isolates belong to genotype 4, subgenotype 4d. These results suggest a potential risk of zoonotic transmission of HEV from younger swine to farmers who rear pigs.

  17. Nucleotide sequences of 16 transmissible plasmids identified in nine multidrug-resistant Escherichia coli isolates expressing an ESBL phenotype isolated from food-producing animals and healthy humans.

    PubMed

    Wang, Juan; Stephan, Roger; Power, Karen; Yan, Qiongqiong; Hächler, Herbert; Fanning, Séamus

    2014-10-01

    Nine extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolated from healthy humans and food-producing animals were found to transfer their cefotaxime resistance marker at high frequency in laboratory conjugation experiments. The objective of this study was to completely characterize 16 transmissible plasmids that were detected in these bacterial isolates. The nucleotide sequences of all 16 plasmids were determined from transconjugants using next-generation sequencing technology. Open reading frames were assigned using Rapid Annotation using Subsystem Technology and analysed by BLASTn and BLASTp. The standard method was used for plasmid multilocus sequence typing (pMLST) analysis. Plasmid structures were subsequently confirmed by PCR amplification of selected regions. The complete circularized nucleotide sequence of 14 plasmids was determined, along with that of a further two plasmids that could not be confirmed as closed. These ranged in size from 1.8 to 166.6 kb. Incompatibility groups and pMLSTs identified included IncI1/ST3, IncI1/ST36, IncN/ST1, IncF and IncB/O, and those of the same Inc types presented a similar backbone structure despite being isolated from different sources. Eight plasmids contained bla(CTX-M-1) genes that were associated with either ISEcp1 or IS26 insertion sequence elements. Six plasmids isolated from humans and chickens were identical or closely related to the IncI1 reference plasmid, R64. These data, based on comparative sequence analysis, highlight the successful spread of blaESBL-harbouring plasmids of different Inc types among isolates of human and food-producing animal origin and provide further evidence for potential dissemination routes. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. 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

    Yoshioka, Miyako; Matsuura, Yuichi; Okada, Hiroyuki; Shimozaki, Noriko; Yamamura, Tomoaki; Murayama, Yuichi; Yokoyama, Takashi; Mohri, Shirou

    2013-07-09

    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. 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. 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.

  19. 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

  20. 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.

  1. Descriptive epidemiological features of cases of bovine spongiform encephalopathy born after July 31, 1996 in Great Britain.

    PubMed

    Wilesmith, J W; Ryan, J B M; Arnold, M E; Stevenson, M A; Burke, P J

    2010-08-21

    This paper describes the results of analyses of the epidemiological features of the 164 cases of bovine spongiform encephalopathy (BSE) in Great Britain that were born after the introduction of the reinforced legislation introduced on August 1, 1996 (BARB cases) and that were detected before December 31, 2008. This additional control measure prohibited the use of mammalian meat and bone meal (MMBM) in feed for farm animals to prevent further exposure of cattle to the BSE agent. There was a pronounced reduction in the risk of infection, by three orders of magnitude, for cattle born after July 31, 1996 compared with that for cattle born earlier, and a statistically significant exponential reduction in the estimated prevalence between successive annual birth cohorts after this date. There was no evidence that a significant number of these cases occurred as a result of a maternally associated risk factor, infection from environmental contamination (other than from feedstuffs) or as a result of a genetically based aetiology. The epidemiological features were consistent with an exogenous feedborne source as a result of a reliance on imported feedstuffs in Great Britain and the later introduction of a ban on the use of MMBM in other EU member states on January 1, 2001.

  2. Neuroanatomical distribution of disease-associated prion protein in experimental bovine spongiform encephalopathy in cattle after intracerebral inoculation.

    PubMed

    Fukuda, Shigeo; Onoe, Sadao; Nikaido, Satoshi; Fujii, Kei; Kageyama, Soichi; Iwamaru, Yoshifumi; Imamura, Morikazu; Masujin, Kentaro; Matsuura, Yuichi; Shimizu, Yoshihisa; Kasai, Kazuo; Yoshioka, Miyako; Murayama, Yuichi; Mohri, Shirou; Yokoyama, Takashi; Okada, Hiroyuki

    2012-01-01

    The pathologic disease-associated prion protein (PrP(Sc)) has been shown to be expressed in the central nervous system of Holstein cattle inoculated intracerebrally with 3 sources of classical bovine spongiform encephalopathy (BSE) isolates. Several regions of the brain and spinal cord were analyzed for PrP(Sc) expression by immunohistochemical and Western blotting analyses. Animals euthanized at 10 months post-inoculation (mpi) showed PrP(Sc) deposits in the brainstem and thalamus, but no vacuolation; this suggested that the BSE agent might exhibit area-dependent tropism in the brain. At 16 and 18 mpi, a small amount of vacuolation was detected in the brainstem and thalamus, but not in the cerebral cortices. At 20 to 24 mpi, when clinical symptoms were apparent, heavy PrP(Sc) deposits were evident throughout the brain and spinal cord. The mean time to the appearance of clinical symptoms was 19.7 mpi, and the mean survival time was 22.7 mpi. These findings show that PrP(Sc) accumulation was detected approximately 10 months before the clinical symptoms of BSE became apparent. In addition, the 3 sources of BSE prion induced no detectable differences in the clinical signs, incubation periods, neuroanatomical location of vacuoles, or distribution and pattern of PrP(Sc) depositions in the brain.

  3. Clinical and Pathologic Features of H-Type Bovine Spongiform Encephalopathy Associated with E211K Prion Protein Polymorphism

    PubMed Central

    Greenlee, Justin J.; Smith, Jodi D.; West Greenlee, M. Heather; Nicholson, Eric M.

    2012-01-01

    The majority of bovine spongiform encephalopathy (BSE) cases have been ascribed to the classical form of the disease. H-type and L-type BSE cases have atypical molecular profiles compared to classical BSE and are thought to arise spontaneously. However, one case of H-type BSE was associated with a heritable E211K mutation in the prion protein gene. The purpose of this study was to describe transmission of this unique isolate of H-type BSE when inoculated into a calf of the same genotype by the intracranial route. Electroretinograms were used to demonstrate preclinical deficits in retinal function, and optical coherence tomography was used to demonstrate an antemortem decrease in retinal thickness. The calf rapidly progressed to clinical disease (9.4 months) and was necropsied. Widespread distribution of abnormal prion protein was demonstrated within neural tissues by western blot and immunohistochemistry. While this isolate is categorized as BSE-H due to a higher molecular mass of the unglycosylated PrPSc isoform, a strong labeling of all 3 PrPSc bands with monoclonal antibodies 6H4 and P4, and a second unglycosylated band at approximately 14 kDa when developed with antibodies that bind in the C-terminal region, it is unique from other described cases of BSE-H because of an additional band 23 kDa demonstrated on western blots of the cerebellum. This work demonstrates that this isolate is transmissible, has a BSE-H phenotype when transmitted to cattle with the K211 polymorphism, and has molecular features that distinguish it from other cases of BSE-H described in the literature. PMID:22715405

  4. Clinical and pathologic features of H-type bovine spongiform encephalopathy associated with E211K prion protein polymorphism.

    PubMed

    Greenlee, Justin J; Smith, Jodi D; West Greenlee, M Heather; Nicholson, Eric M

    2012-01-01

    The majority of bovine spongiform encephalopathy (BSE) cases have been ascribed to the classical form of the disease. H-type and L-type BSE cases have atypical molecular profiles compared to classical BSE and are thought to arise spontaneously. However, one case of H-type BSE was associated with a heritable E211K mutation in the prion protein gene. The purpose of this study was to describe transmission of this unique isolate of H-type BSE when inoculated into a calf of the same genotype by the intracranial route. Electroretinograms were used to demonstrate preclinical deficits in retinal function, and optical coherence tomography was used to demonstrate an antemortem decrease in retinal thickness. The calf rapidly progressed to clinical disease (9.4 months) and was necropsied. Widespread distribution of abnormal prion protein was demonstrated within neural tissues by western blot and immunohistochemistry. While this isolate is categorized as BSE-H due to a higher molecular mass of the unglycosylated PrP(Sc) isoform, a strong labeling of all 3 PrP(Sc) bands with monoclonal antibodies 6H4 and P4, and a second unglycosylated band at approximately 14 kDa when developed with antibodies that bind in the C-terminal region, it is unique from other described cases of BSE-H because of an additional band 23 kDa demonstrated on western blots of the cerebellum. This work demonstrates that this isolate is transmissible, has a BSE-H phenotype when transmitted to cattle with the K211 polymorphism, and has molecular features that distinguish it from other cases of BSE-H described in the literature.

  5. Cows for fear: is BSE a threat to human health? Bovine spongiform encephalopathy.

    PubMed Central

    Josephson, J

    1998-01-01

    In 1996, a new variant of Creutzfeldt-Jakob disease (vCJD)-a disease that causes lack of coordination, muscle twitching or jerking, dementia, and, eventually, death-suddenly appeared in Great Britain. It is believed that the victims contracted the disease from eating the beef of cattle stricken with bovine spongiform encephalopathy (BSE), or mad cow disease. As of December 1997, at least 25 people in the United Kingdom and France have contracted vCJD. PMID:9485478

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

    USDA-ARS?s Scientific Manuscript database

    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...

  7. Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie

    PubMed Central

    Houston, Fiona; Goldmann, Wilfred; Foster, James; González, Lorenzo; Jeffrey, Martin; Hunter, Nora

    2015-01-01

    Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE), which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock). The unusually long observation period (6–8 years for most, but up to 12 years for others) allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of sheep is moved

  8. Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie.

    PubMed

    Houston, Fiona; Goldmann, Wilfred; Foster, James; González, Lorenzo; Jeffrey, Martin; Hunter, Nora

    2015-01-01

    Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE), which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock). The unusually long observation period (6-8 years for most, but up to 12 years for others) allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of sheep is moved

  9. Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent

    PubMed Central

    2010-01-01

    Background Various clinical protocols have been developed to aid in the clinical diagnosis of classical bovine spongiform encephalopathy (BSE), which is confirmed by postmortem examinations based on vacuolation and accumulation of disease-associated prion protein (PrPd) in the brain. The present study investigated the occurrence and progression of sixty selected clinical signs and behaviour combinations in 513 experimentally exposed cattle subsequently categorised postmortem as confirmed or unconfirmed BSE cases. Appropriate undosed or saline inoculated controls were examined similarly and the data analysed to explore the possible occurrence of BSE-specific clinical expression in animals unconfirmed by postmortem examinations. Results Based on the display of selected behavioural, sensory and locomotor changes, 20 (67%) orally dosed and 17 (77%) intracerebrally inoculated pathologically confirmed BSE cases and 21 (13%) orally dosed and 18 (6%) intracerebrally inoculated but unconfirmed cases were considered clinical BSE suspects. None of 103 controls showed significant signs and were all negative on diagnostic postmortem examinations. Signs indicative of BSE suspects, particularly over-reactivity and ataxia, were more frequently displayed in confirmed cases with vacuolar changes in the brain. The display of several BSE-associated signs over time, including repeated startle responses and nervousness, was significantly more frequent in confirmed BSE cases compared to controls, but these two signs were also significantly more frequent in orally dosed cattle unconfirmed by postmortem examinations. Conclusions The findings confirm that in experimentally infected cattle clinical abnormalities indicative of BSE are accompanied by vacuolar changes and PrPd accumulation in the brainstem. The presence of more frequently expressed signs in cases with vacuolar changes is consistent with this pathology representing a more advanced stage of disease. That BSE-like signs or sign

  10. Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent.

    PubMed

    Konold, Timm; Sayers, A Robin; Sach, Amanda; Bone, Gemma E; van Winden, Steven; Wells, Gerald A H; Simmons, Marion M; Stack, Michael J; Wear, Angus; Hawkins, Steve A C

    2010-12-09

    Various clinical protocols have been developed to aid in the clinical diagnosis of classical bovine spongiform encephalopathy (BSE), which is confirmed by postmortem examinations based on vacuolation and accumulation of disease-associated prion protein (PrPd) in the brain. The present study investigated the occurrence and progression of sixty selected clinical signs and behaviour combinations in 513 experimentally exposed cattle subsequently categorised postmortem as confirmed or unconfirmed BSE cases. Appropriate undosed or saline inoculated controls were examined similarly and the data analysed to explore the possible occurrence of BSE-specific clinical expression in animals unconfirmed by postmortem examinations. Based on the display of selected behavioural, sensory and locomotor changes, 20 (67%) orally dosed and 17 (77%) intracerebrally inoculated pathologically confirmed BSE cases and 21 (13%) orally dosed and 18 (6%) intracerebrally inoculated but unconfirmed cases were considered clinical BSE suspects. None of 103 controls showed significant signs and were all negative on diagnostic postmortem examinations. Signs indicative of BSE suspects, particularly over-reactivity and ataxia, were more frequently displayed in confirmed cases with vacuolar changes in the brain. The display of several BSE-associated signs over time, including repeated startle responses and nervousness, was significantly more frequent in confirmed BSE cases compared to controls, but these two signs were also significantly more frequent in orally dosed cattle unconfirmed by postmortem examinations. The findings confirm that in experimentally infected cattle clinical abnormalities indicative of BSE are accompanied by vacuolar changes and PrPd accumulation in the brainstem. The presence of more frequently expressed signs in cases with vacuolar changes is consistent with this pathology representing a more advanced stage of disease. That BSE-like signs or sign combinations occur in inoculated

  11. 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

  12. Quantifying the relative amounts of PrP polymorphisms present in prions isolated from heterozygous prion-infected animals

    USDA-ARS?s Scientific Manuscript database

    Prions cause protein misfolding diseases, such as transmissible spongiform encephalopathy. They propagate infections by converting a normal cellular prion protein into a prion (PrPSc). PrPC and PrPSc are isosequential and differ only in their respective conformations. PrPC is monomeric and sensit...

  13. Biological and biochemical characterization of L-type-like bovine spongiform encephalopathy (BSE) detected in Japanese black beef cattle

    PubMed Central

    Masujin, Kentaro; Shu, Yujing; Yamakawa, Yoshio; Hagiwara, Ken'ichi; Sata, Tetsutaro; Matsuura, Yuichi; Iwamaru, Yoshifumi; Imamura, Morikazu; Okada, Hiroyuki; Mohri, Shirou

    2008-01-01

    A case of L-type-like atypical bovine spongiform encephalopathy was detected in 14-year-old Japanese black beef cattle (BSE/JP24). To clarify the biological and biochemical properties of the prion in BSE/JP24, we performed a transmission study with wild-type mice and bovinized transgenic mice (TgBoPrP). The BSE/JP24 prion was transmitted to TgBoPrP mice with the incubation period of 199.7 ± 3.4 days, which was shorter than that of classical BSE (C-BSE) (223.5 ± 13.5 days). Further, C-BSE was transmitted to wild-type mice with the incubation period of about 409 days, whereas BSE/JP24 prion inoculated mice showed no clinical signs up to 649 days. Severe vacuolation and a widespread and uniform distribution of PrPSc were pathologically observed in the brain of BSE/JP24 prion affected TgBoPrP mice. The molecular weight and glycoform ratio of PrPSc in BSE/JP24 were different from those in C-BSE, and PrPSc in BSE/JP24 exhibited weaker proteinase K resistance than that in C-BSE. These findings revealed that the BSE/JP24 prion has distinct biological and biochemical properties reported for that of C-BSE. Interestingly, a shorter incubation period was observed at the subsequent passage of the BSE/JP24 prion to TgBoPrP mice (152.2 ± 3.1 days). This result implies that BSE/JP24 prion has newly emerged and showed the possibility that L-type BSE prion might be classified into multiple strains. PMID:19158500

  14. 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.

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

    USGS Publications Warehouse

    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.

  16. 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

  17. The pathological and molecular but not clinical phenotypes are maintained after second passage of experimental atypical bovine spongiform encephalopathy in cattle.

    PubMed

    Konold, Timm; Phelan, Laura J; Clifford, Derek; Chaplin, Melanie J; Cawthraw, Saira; Stack, Michael J; Simmons, Marion M

    2014-10-02

    Atypical bovine spongiform encephalopathies (BSEs), classified as H-type and L-type BSE based on the Western immunoblot profiles, are naturally occurring diseases in cattle, which are phenotypically different to classical BSE. Transmission studies in cattle using the intracerebral route resulted in disease where the phenotypes were maintained irrespective of BSE type but clinically affected cattle with a shorter survival time displayed a nervous form whereas cattle with a longer survival time displayed a dull form. A second transmission study is reported here where four cattle were intracerebrally inoculated with brain tissue from experimentally infected cattle presenting with either the nervous or dull form of H- or L-type BSE to determine whether the phenotype is maintained. The four inoculated cattle were culled at 16.5-19.5 months post inoculation after presenting with difficulty getting up, a positive scratch response (all) and dullness (three cattle), which was not observed in two non-inoculated control cattle, each housed with either group of inoculated cattle. Only the inoculated cattle had detectable prion protein in the brain based on immunohistochemical examination, and the Western immunoblot profile was consistent with the H-type or L-type BSE of the respective donor cattle. Second passage of H-type and L-type BSE in cattle produced a TSE where the majority of cattle displayed the dull form regardless of clinical disease form of the donor cattle. The pathological and molecular phenotypes of H- and L-type BSE were maintained.

  18. Detection and partial discrimination of atypical and classical bovine spongiform encephalopathies in cattle and primates using real-time quaking-induced conversion assay.

    PubMed

    Levavasseur, Etienne; Biacabe, Anne-Gaëlle; Comoy, Emmanuel; Culeux, Audrey; Grznarova, Katarina; Privat, Nicolas; Simoneau, Steve; Flan, Benoit; Sazdovitch, Véronique; Seilhean, Danielle; Baron, Thierry; Haïk, Stéphane

    2017-01-01

    The transmission of classical bovine spongiform encephalopathy (C-BSE) through contaminated meat product consumption is responsible for variant Creutzfeldt-Jakob disease (vCJD) in humans. More recent and atypical forms of BSE (L-BSE and H-BSE) have been identified in cattle since the C-BSE epidemic. Their low incidence and advanced age of onset are compatible with a sporadic origin, as are most cases of Creutzfeldt-Jakob disease (CJD) in humans. Transmissions studies in primates and transgenic mice expressing a human prion protein (PrP) indicated that atypical forms of BSE may be associated with a higher zoonotic potential than classical BSE, and require particular attention for public health. Recently, methods designed to amplify misfolded forms of PrP have emerged as promising tools to detect prion strains and to study their diversity. Here, we validated real-time quaking-induced conversion assay for the discrimination of atypical and classical BSE strains using a large series of bovine samples encompassing all the atypical BSE cases detected by the French Centre of Reference during 10 years of exhaustive active surveillance. We obtained a 100% sensitivity and specificity for atypical BSE detection. In addition, the assay was able to discriminate atypical and classical BSE in non-human primates, and also sporadic CJD and vCJD in humans. The RT-QuIC assay appears as a practical means for a reliable detection of atypical BSE strains in a homologous or heterologous PrP context.

  19. Chronic wasting disease and atypical forms of BSE and scrapie are not transmissible to mice expressing wild-type levels of human PrP

    USDA-ARS?s Scientific Manuscript database

    The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) has demonstrated that cattle 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 new TSEs in shee...

  20. Primary transmission of chronic wasting disease versus scrapie prions from small ruminants to transgenic mice expressing ovine and cervid prion protein

    USDA-ARS?s Scientific Manuscript database

    Identifying transmissible spongiform encephalopathy (TSE) reservoirs that could lead to disease re-emergence is imperative to U.S. scrapie eradication efforts. Transgenic mice expressing the cervid (TgElk) or ovine (Tg338) prion protein have aided characterization of chronic wasting disease (CWD) an...

  1. Modelling the trend of bovine spongiform encephalopathy prevalence in France: Use of restricted cubic spline regression in age-period-cohort models to estimate the efficiency of control measures.

    PubMed

    Sala, Carole; Morignat, Eric; Ducrot, Christian; Calavas, Didier

    2009-07-01

    An age-period-cohort (APC) analysis was used to assess the trend in prevalence of bovine spongiform encephalopathy (BSE) in France over time in relation to the control measures adopted since onset of the epidemic. Restricted cubic regression splines were used to model the functional forms of the non-linear effects of age at screening, birth cohort and date of diagnosis of the tested animals. The data of the 2001-2007 period of surveillance was analysed using 1-year categorisation. A categorical analysis was performed as control to check the accuracy of the sets of knots in the spline models, which were selected according to the Akaike Information Criterion (AIC). Knot selection was based on a priori knowledge of the disease and the dates of implementation of the five main BSE control measures. It was assumed that disease prevalence was a function of exposure to BSE and that changes in the exposure of cattle to BSE were mainly due to the control measures. The effects of the five main control measures were discussed in relation to the trend in BSE risk for the successive birth cohorts. The six selected models confirmed that all measures participated in disease control. However, characterization of the respective effect of individual measures was not straightforward due to the very low disease prevalence, incompletely tested cohorts and probably cumulative and overlapping effects of successive measures. The ban of importation of meat and bone meal (MBM) from the UK and the ban of use of MBM in bovines were insufficient to control the epidemic. The decline in the BSE epidemic more likely originated from implementation of the ban of MBM use in all ruminants in 1994, whose effect was probably reinforced by the evolution in perception of the BSE risk following evidence of BSE transmission to humans. Finally, the respective effects of the last two measures (prohibition of the use of specific risk material in 1996 and total MBM ban in 2000) could not be characterized as

  2. Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in Endodontic Practice in Absence of Adequate Prion Inactivation

    PubMed Central

    Bourvis, Nadège; Boelle, Pierre-Yves; Cesbron, Jean-Yves; Valleron, Alain-Jacques

    2007-01-01

    Background Experimental results evidenced the infectious potential of the dental pulp of animals infected with transmissible spongiform encephalopathies (TSE). This route of iatrogenic transmission of sporadic Creutzfeldt-Jakob disease (sCJD) may exist in humans via reused endodontic instruments if inadequate prion decontamination procedures are used. Methodology/Principal Findings To assess this risk, 10 critical parameters in the transmission process were identified, starting with contamination of an endodontic file during treatment of an infectious sCJD patient and ending with possible infection of a subsequent susceptible patient. It was assumed that a dose-risk response existed, with no-risk below threshold values. Plausible ranges of those parameters were obtained through literature search and expert opinions, and a sensitivity analysis was conducted. Without effective prion-deactivation procedures, the risk of being infected during endodontic treatment ranged between 3.4 and 13 per million procedures. The probability that more than one case was infected secondary to endodontic treatment of an infected sCJD patient ranged from 47% to 77% depending on the assumed quantity of infective material necessary for disease transmission. If current official recommendations on endodontic instrument decontamination were strictly followed, the risk of secondary infection would become quasi-null. Conclusion The risk of sCJD transmission through endodontic procedure compares with other health care risks of current concern such as death after liver biopsy or during general anaesthesia. These results show that single instrument use or adequate prion-decontamination procedures like those recently implemented in dental practice must be rigorously enforced. PMID:18159228

  3. Risk assessment of transmission of sporadic Creutzfeldt-Jakob disease in endodontic practice in absence of adequate prion inactivation.

    PubMed

    Bourvis, Nadège; Boelle, Pierre-Yves; Cesbron, Jean-Yves; Valleron, Alain-Jacques

    2007-12-26

    Experimental results evidenced the infectious potential of the dental pulp of animals infected with transmissible spongiform encephalopathies (TSE). This route of iatrogenic transmission of sporadic Creutzfeldt-Jakob disease (sCJD) may exist in humans via reused endodontic instruments if inadequate prion decontamination procedures are used. To assess this risk, 10 critical parameters in the transmission process were identified, starting with contamination of an endodontic file during treatment of an infectious sCJD patient and ending with possible infection of a subsequent susceptible patient. It was assumed that a dose-risk response existed, with no-risk below threshold values. Plausible ranges of those parameters were obtained through literature search and expert opinions, and a sensitivity analysis was conducted. Without effective prion-deactivation procedures, the risk of being infected during endodontic treatment ranged between 3.4 and 13 per million procedures. The probability that more than one case was infected secondary to endodontic treatment of an infected sCJD patient ranged from 47% to 77% depending on the assumed quantity of infective material necessary for disease transmission. If current official recommendations on endodontic instrument decontamination were strictly followed, the risk of secondary infection would become quasi-null. The risk of sCJD transmission through endodontic procedure compares with other health care risks of current concern such as death after liver biopsy or during general anaesthesia. These results show that single instrument use or adequate prion-decontamination procedures like those recently implemented in dental practice must be rigorously enforced.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  5. Exploring the risks of a putative transmission of BSE to new species

    PubMed Central

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

    2013-01-01

    The prion responsible for the Bovine Spongiform Encephalopathy (BSE) shows unique features when compared with other prions. One of these features is its ability to infect almost all experimentally tested animal models. In the paper published in The Journal of Neuroscience1 we describe a series of experiments directed toward elucidating which would be the in vivo behavior of BSE if it would infect dogs and rabbits, two alleged prion resistant species. Protein misfolding cyclic amplification (PMCA) was used to generate canidae and leporidae in vitro adapted BSE prions. A characterization of their in vivo pathobiological properties showed that BSE prions were capable not only of adapting to new species but they maintained, in the case of rabbits, their ability to infect transgenic mice expressing human PrP. The remarkable adaptation ability of certain prions implies that any new host species could lead to the emergence of new infectious agents with unpredictable transmission potential. Our results suggest that caution must be taken when considering the use of any mammal-derived protein in feedstuffs. PMID:24184875

  6. Authentication of meat and meat products vs. detection of animal species in feed – what is the difference?

    NASA Astrophysics Data System (ADS)

    Nešić, K.; Stojanović, D.; Baltić, Ž. M.

    2017-09-01

    Authenticity of food is an issue that is growing in awareness and concern. Although food adulteration has been present since antiquity, it has broadened to include entire global populations as modern food supply chains have expanded, enriched and become more complex. Different forms of adulteration influence not only the quality of food products, but also may cause harmful health effects. Meat and meat products are often subjected to counterfeiting, mislabelling and similar fraudulent activities, while substitutions of meat ingredients with other animal species is one among many forms of food fraud. Feed is also subject to testing for the presence of different animal species, but as part of the eradication process of transmissible spongiform encephalopathies (TSE). In both food and feed cases, the final goal is consumer protection, which should be provided by quick, precise and specific tools. Several analytical tests have been employed for such needs. This paper provides an overview of authentication of meat and meat products compared with species identification in feed control, highlighting the most prevalent laboratory methods.

  7. Transmission of chronic wasting disease of mule deer to Suffolk sheep following intracerebral inoculation.

    PubMed

    Hamir, Amir N; Kunkle, Robert A; Cutlip, Randall C; Miller, Janice M; Williams, Elizabeth S; Richt, Juergen A

    2006-11-01

    To determine the transmissibility of chronic wasting disease (CWD) to sheep, 8 Suffolk lambs of various prion protein genotypes (4 ARQ/ARR, 3 ARQ/ARQ, 1 ARQ/VRQ at codons 136, 154, and 171, respectively) were inoculated intracerebrally with brain suspension from mule deer with CWD (CWDmd). Two other lambs were kept as noninoculated controls. Within 36 months postinoculation (MPI), 2 inoculated animals became sick and were euthanized. Only 1 sheep (euthanized at 35 MPI) showed clinical signs that were consistent with those described for scrapie. Microscopic lesions of spongiform encephalopathy (SE) were only seen in this sheep, and its tissues were determined to be positive for the abnormal prion protein (PrP(res)) by immunohistochemistry and Western blot. Three other inoculated sheep were euthanized (36 to 60 MPI) because of conditions unrelated to TSE. The 3 remaining inoculated sheep and the 2 control sheep did not have clinical signs of disease at the termination of the study (72 MPI) and were euthanized. Of the 3 remaining inoculated sheep, 1 was found to have SE, and its tissues were positive for PrP(res). The sheep with clinical prion disease (euthanized at 35 MPI) was of the heterozygous genotype (ARQ/VRQ), and the sheep with subclinical disease (euthanized at 72 MPH) was of the homozygous ARQ/ARQ genotype. These findings demonstrate that transmission of the CWDmd agent to sheep via the intracerebral route is possible. Interestingly, the host genotype may play a notable part in successful transmission and incubation period of CWDmd.

  8. Atypical variants of bovine spongiform encephalopathy: rare diseases with consequences for BSE surveillance and control.

    PubMed

    Boujon, C; Serra, F; Seuberlich, T

    2016-03-01

    Occurring for the first time in 1986 in the United Kingdom, bovine spongiform encephalopathy (BSE), the so-called "mad-cow disease", has had unprecedented consequences in veterinary public health. The implementation of drastic measures, including the ban of meat-and-bone-meal from livestock feed and the removal of specified risk materials from the food chain has eventually resulted in a significant decline of the epidemic. The disease was long thought to be caused by a single agent, but since the introduction of immunochemical diagnostic techniques, evidence of a phenotypic variation of BSE has emerged. Reviewing the literature available on the subject, this paper briefly summarizes the current knowledge about these atypical forms of BSE and discusses the consequences of their occurrence for disease control measures.

  9. Polymorphism of the prion protein gene (PRNP) in Polish cattle affected by classical bovine spongiform encephalopathy.

    PubMed

    Gurgul, Artur; Czarnik, Urszula; Urszula, Czarnik; Larska, Magdalena; Polak, Mirosław P; Strychalski, Janusz; Słota, Ewa

    2012-05-01

    Recent attempts to discover genetic factors affecting cattle resistance/susceptibility to bovine spongiform encephalopathy (BSE) have led to the identification of two insertion/deletion (indel) polymorphisms, located within the promoter and intron 1 of the prion protein gene PRNP, showing a significant association with the occurrence of classical form of the disease. Because the effect of the polymorphisms was studied only in few populations, in this study we investigated whether previously described association of PRNP indel polymorphisms with BSE susceptibility in cattle is also present in Polish cattle population. We found a significant relation between the investigated PRNP indel polymorphisms (23 and 12 bp indels), and susceptibility of Polish Holstein-Friesian cattle to classical BSE (P < 0.05). The deletion variants of both polymorphisms were related to increased susceptibility, whereas insertion variants were protective against BSE.

  10. Detection of bovine central nervous system tissue as bovine spongiform encephalopathy risk material by real-time reverse transcriptase-PCR in raw and cooked beef products.

    PubMed

    Shi, Xi-Ju; Ma, Gui-Ping; Li, Bing-Ling; Yang, Jin-Liang; Yu-Wang; Li, Yan-Xin; Liu, Xu-Hui; Liu, Quan-Guo

    2008-01-01

    There is increasing evidence of the association of the new variant of Creutzfeldt-Jacob disease (nvCJD) in humans with bovine spongiform encephalopathy (BSE) in cattle. Many countries established legislation of banning central nervous system (CNS) tissues, which are regarded as BSE-specified risk materials (SRM), in human food supply because of the potential transmission of BSE to humans. A real-time reverse transcriptase-PCR assay using the bovine glial fibrillary acidic protein (GFAP) mRNA template for the detection of CNS tissues in raw and cooked beef products was developed in this study. The results showed that (1) this method can detect CNS tissues from bovine and ovine origins, but not from porcine and avian ones; (2) GFAP mRNA can only be detected from brain and spinal cords rather than other tissues; (3) the GFAP mRNA was detectable in CNS tissues even after dilution to 0.001%; and (4) the assay was unaffected by heat treatment at 100 degrees C for 30 min or storage at room temperature for 4 days, and at 4 degrees C for at least 15 days.

  11. 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

  12. A case of spongiform polioencephalomyelopathy in a cat with a history of behavioural problems.

    PubMed

    Camps, Tomàs; de la Fuente, Cristian; Pumarola, Martí; Amat, Marta; Le Brech, Susana; Manteca, Xavier

    2015-01-01

    A 7-month-old, entire female, domestic shorthair cat was referred to our behavioural service owing to soiling in the house and a play-related problem. The owners' complaints were that the cat had never used the litter tray, and it did not know how to play. After reviewing the behavioural history, a problem of substrate preferences acquisition was suspected with regard to the elimination problem. During the consultation, the physical examination was unremarkable, but the neurological examination revealed a moderate and hypermetric ataxic gait, and a bilateral lack of menace response. Some degree of visual impairment was suspected. The problem was located in the central nervous system (CNS); specifically, an intracranial and multifocal problem was diagnosed. After a complete work-up (complete ophthalmological examination, complete blood count and a complete biochemistry panel, feline immunodeficiency virus/feline leukaemia virus test, thorax radiographs, abdominal ultrasound, brain magnetic resonance imaging [0.2 T], cerebrospinal fluid analysis and a urinary metabolic screen test), a degenerative CNS problem was suspected. No treatment was prescribed for the neurological problem. Regarding the problem of soiling in the house, reward-based training with a clicker was used, and the cat partially improved in a few weeks. Three months later, the cat was referred to the neurology service in status epilepticus. A symptomatic treatment was prescribed, with a mild response. After 2 years of treatment and a progressive worsening, the cat was euthanased. Necropsy revealed spongiform polioencephalomyelopathy. In order to rule out prion aetiology a PrPsc inmunohistochemistry assay was performed, and the results were negative. Congenital spongiform polioencephalomyelopathy (CSP) was diagnosed. We strongly suggest that the cat's behavioural clinical signs were caused by the CSP, causing learning impairment. To the best of our knowledge, this would be the first case in which a

  13. Bordetella pertussis transmission.

    PubMed

    Trainor, Elizabeth A; Nicholson, Tracy L; Merkel, Tod J

    2015-11-01

    Bordetella pertussis and B. bronchiseptica are Gram-negative bacterial respiratory pathogens. Bordetella pertussis is the causative agent of whooping cough and is considered a human-adapted variant of B. bronchiseptica. Bordetella pertussis and B. bronchiseptica share mechanisms of pathogenesis and are genetically closely related. However, despite the close genetic relatedness, these Bordetella species differ in several classic fundamental aspects of bacterial pathogens such as host range, pathologies and persistence. The development of the baboon model for the study of B. pertussis transmission, along with the development of the swine and mouse model for the study of B. bronchiseptica, has enabled the investigation of different aspects of transmission including the route, attack rate, role of bacterial and host factors, and the impact of vaccination on transmission. This review will focus on B. pertussis transmission and how animal models of B. pertussis transmission and transmission models using the closely related B. bronchiseptica have increased our understanding of B. pertussis transmission.

  14. Highly pathogenic avian influenza A(H5N1) mutants transmissible by air are susceptible to human and animal neutralizing antibodies.

    PubMed

    Du, Lanying; Li, Ye; Zhao, Guangyu; Wang, Lili; Zou, Peng; Lu, Lu; Zhou, Yusen; Jiang, Shibo

    2013-10-15

    A laboratory-generated reassortant H5 hemagglutinin (HA)/influenza A(H1N1) strain containing 4 mutations in influenza A(H5N1) HA has become transmissible by air among mammals. Here, we constructed 15 influenza A(H5N1) pseudoviruses containing a single mutation or a combination of mutations and showed that the pseudoviruses were susceptible to neutralizing antibodies from patients with influenza A(H5N1) infection and from mice immunized with a vaccine containing the conserved HA1 sequence of influenza A(H5N1). These results indicate that antibodies in patients currently infected by influenza A(H5N1) and antibodies induced by vaccines containing conserved sequences in HA1 of wild-type influenza A(H5N1) are highly effective in cross-neutralizing future influenza A(H5N1) mutants with airborne transmissibility, suggesting that human influenza pandemics caused by these influenza A(H5N1) variants can be prevented.

  15. Animal communication.

    PubMed

    Kaplan, Gisela

    2014-11-01

    Animal communication is first and foremost about signal transmission and aims to understand how communication occurs. It is a field that has contributed to and been inspired by other fields, from information technology to neuroscience, in finding ever better methods to eavesdrop on the actual 'message' that forms the basis of communication. Much of this review deals with vocal communication as an example of the questions that research on communication has tried to answer and it provides an historical overview of the theoretical arguments proposed. Topics covered include signal transmission in different environments and different species, referential signaling, and intentionality. The contention is that animal communication may reveal significant thought processes that enable some individuals in a small number of species so far investigated to anticipate what conspecifics might do, although some researchers think of such behavior as adaptive or worth dismissing as anthropomorphizing. The review further points out that some species are more likely than others to develop more complex communication patterns. It is a matter of asking how animals categorize their world and which concepts require cognitive processes and which are adaptive. The review concludes with questions of life history, social learning, and decision making, all criteria that have remained relatively unexplored in communication research. Long-lived, cooperative social animals have so far offered especially exciting prospects for investigation. There are ample opportunities and now very advanced technologies as well to tap further into expressions of memory of signals, be they vocal or expressed in other modalities. WIREs Cogn Sci 2014, 5:661-677. doi: 10.1002/wcs.1321 For further resources related to this article, please visit the WIREs website. The author has declared no conflicts of interest for this article. © 2014 John Wiley & Sons, Ltd.

  16. Animal Reservoir, Natural and Socioeconomic Variations and the Transmission of Hemorrhagic Fever with Renal Syndrome in Chenzhou, China, 2006–2010

    PubMed Central

    Basta, Nicole; Cazelles, Bernard; Li, Xiu-Jun; Lin, Xiao-Ling; Wu, Hong-Wei; Chen, Bi-Yun; Yang, Hui-Suo; Xu, Bing; Grenfell, Bryan

    2014-01-01

    Background China has the highest incidence of hemorrhagic fever with renal syndrome (HFRS) worldwide. Reported cases account for 90% of the total number of global cases. By 2010, approximately 1.4 million HFRS cases had been reported in China. This study aimed to explore the effect of the rodent reservoir, and natural and socioeconomic variables, on the transmission pattern of HFRS. Methodology/Principal Findings Data on monthly HFRS cases were collected from 2006 to 2010. Dynamic rodent monitoring data, normalized difference vegetation index (NDVI) data, climate data, and socioeconomic data were also obtained. Principal component analysis was performed, and the time-lag relationships between the extracted principal components and HFRS cases were analyzed. Polynomial distributed lag (PDL) models were used to fit and forecast HFRS transmission. Four principal components were extracted. Component 1 (F1) represented rodent density, the NDVI, and monthly average temperature. Component 2 (F2) represented monthly average rainfall and monthly average relative humidity. Component 3 (F3) represented rodent density and monthly average relative humidity. The last component (F4) represented gross domestic product and the urbanization rate. F2, F3, and F4 were significantly correlated, with the monthly HFRS incidence with lags of 4 months (r = −0.289, P<0.05), 5 months (r = −0.523, P<0.001), and 0 months (r = −0.376, P<0.01), respectively. F1 was correlated with the monthly HFRS incidence, with a lag of 4 months (r = 0.179, P = 0.192). Multivariate PDL modeling revealed that the four principal components were significantly associated with the transmission of HFRS. Conclusions The monthly trend in HFRS cases was significantly associated with the local rodent reservoir, climatic factors, the NDVI, and socioeconomic conditions present during the previous months. The findings of this study may facilitate the development of early warning systems for the

  17. Rapid fingerprinting of sterols and related compounds in vegetable and animal oils and phytosterol enriched- margarines by transmission mode direct analysis in real time mass spectrometry.

    PubMed

    Alberici, Rosana M; Fernandes, Gabriel D; Porcari, Andréia M; Eberlin, Marcos N; Barrera-Arellano, Daniel; Fernández, Facundo M

    2016-11-15

    Plant-derived sterols, often referred to as phytosterols, are important constituents of plant membranes where they assist in maintaining phospholipid bilayer stability. Consumption of phytosterols has been suggested to positively affect human health by reducing cholesterol levels in blood via inhibition of its absorption in the small intestine, thus protecting against heart attack and stroke. Sterols are challenging analytes for mass spectrometry, since their low polarity makes them difficult to ionize by both electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI), typically requiring derivatization steps to overcome their low ionization efficiencies. We present a fast and reliable method to characterize the composition of phytosterols in vegetable oils and enriched margarines. The method requires no derivatization steps or sample extraction procedures thanks to the use of transmission mode direct analysis in real time mass spectrometry (TM-DART-MS).

  18. Oolong tea extract as a substitute for uranyl acetate in staining of ultrathin sections based on examples of animal tissues for transmission electron microscopy.

    PubMed

    He, Xiaohua; Liu, Bin

    2017-03-20

    Oolong tea extract (OTE) was assessed for its potential as an electron stain to substitute for uranyl acetate (UA) in transmission electron microscopy (TEM). A comparative analysis of the ultrastructures of biological specimens (i.e. compound eye and sciatic nerve tissue) stained by different methods (UA and 0.1% OTE) has been performed. Results revealed that there was no significant difference between the OTE double staining method and the traditional double staining method, except the contrast in the OTE method was slightly lower than the UA method. Nevertheless, the OTE method yielded better or equal details in collagen fibres, neurofilaments and basal lamina in the mammalian sciatic nerve samples, as well as in the microvilli between the cornea and crystalline cone of the insect compound eye. On the whole, it was suggested that OTE could potentially be used as a nonradioactive and hazard-free alternative to UA in TEM staining.

  19. Neuroanatomical distribution of disease-associated prion protein in cases of bovine spongiform encephalopathy detected by fallen stock surveillance in Japan.

    PubMed

    Okada, Hiroyuki; Iwamaru, Yoshihumi; Imamura, Morikazu; Masujin, Kentaro; Matsuura, Yuichi; Shimizu, Yoshihisa; Kasai, Kazuo; Takata, Masuhiro; Fukuda, Shigeo; Nikaido, Satoshi; Fujii, Kei; Onoe, Sadao; Mohri, Shirou; Yokoyama, Takashi

    2011-11-01

    Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative disorder of cattle characterized by accumulation of the disease-associated prion protein (PrP(Sc)) in the central nervous system (CNS). The immunohistochemical patterns and distribution of PrP(Sc) were investigated in the CNS, brains, and spinal cords of 7 naturally occurring BSE cases confirmed by the fallen stock surveillance program in Japan. No animals showed characteristic clinical signs of the disease. Coronal slices of 14 different brain areas in each case were immunohistochemically analyzed using an anti-prion protein antibody. Immunolabeled PrP(Sc) deposition was widely observed throughout each brain and spinal cord. Intense PrP(Sc) deposition was greater in the thalamus, brainstem, and spinal cord of the gray matter than in the neocortices. The topographical distribution pattern and severity of PrP(Sc) accumulation were mapped and plotted as immunohistochemical profiles of the different brain areas along the caudal-rostral axis of the brain. The distribution pattern and severity of the immunolabeled PrP(Sc) in the CNS were almost the same among the 7 cases analyzed, suggesting that the naturally occurring cases in this study were at the preclinical stage of the disease. Immunohistochemical mapping of the PrP(Sc) deposits will be used to clarify the different stages of BSE in cattle.

  20. Expression of genes involved in the T cell signalling pathway in circulating immune cells of cattle 24 months following oral challenge with Bovine Amyloidotic Spongiform Encephalopathy (BASE).

    PubMed

    Trovato, Andrea; Panelli, Simona; Strozzi, Francesco; Cambulli, Caterina; Barbieri, Ilaria; Martinelli, Nicola; Lombardi, Guerino; Capoferri, Rossana; Williams, John L

    2015-05-09

    Bovine Amyloidotic Spongiform Encephalopathy (BASE) is a variant of classical BSE that affects cows and can be transmitted to primates and mice. BASE is biochemically different from BSE and shares some molecular and histo-pathological features with the MV2 sub-type of human sporadic Creutzfeld Jakob Disease (sCJD). The present work examined the effects of BASE on gene expression in circulating immune cells. Ontology analysis of genes differentially expressed between cattle orally challenged with brain homogenate from cattle following intracranial inoculation with BASE and control cattle identified three main pathways which were affected. Within the immune function pathway, the most affected genes were related to the T cell receptor-mediated T cell activation pathways. The differential expression of these genes in BASE challenged animals at 10,12 and 24 months following challenge, vs unchallenged controls, was investigated by real time PCR. The results of this study show that the effects of prion diseases are not limited to the CNS, but involve the immune system and particularly T cell signalling during the early stage following challenge, before the appearance of clinical signs.

  1. Is there a decline in bovine spongiform encephalopathy cases born after reinforced feed bans? A modelling study in EU member states.

    PubMed

    Arnold, M E; Simons, R R L; Hope, J; Gibbens, N; Adkin, A L

    2017-08-01

    Occasional cases of classical bovine spongiform encephalopathy (BSE) still continue to occur within the European Union (EU) for animals born after reinforced feed bans (BARBs), which should in theory have eliminated all risk of infection. The study aimed to determine (i) whether a common rate of decline of BSE infection was evident across EU member states, i.e. to determine whether control measures have been equally effective in all member states, (ii) whether there was any evidence of spontaneous occurrence of BSE in the data and (iii) the expected date for the last BSE case in UK. It was found that there was no significant difference in the rate of decline of BSE prevalence between member states, with a common rate of decline of 33·9% per annum (95% CI 30·9-37%) in successive annual birth cohorts. Trend analysis indicated an ultimate decline to 0 prevalence, suggesting that spontaneous occurrence does not explain the majority of cases. Projecting forward the trends from the back-calculation model indicated that there was approximately a 50% probability of further cases in the UK, and should the current rate of decline continue, there remains the possibility of further occasional cases up until 2026.

  2. Mapping of neurotrophins and their receptors in the adult mouse brain and their role in the pathogenesis of a transgenic murine model of bovine spongiform encephalopathy.

    PubMed

    Marco-Salazar, P; Márquez, M; Fondevila, D; Rabanal, R M; Torres, J M; Pumarola, M; Vidal, E

    2014-05-01

    Neurotrophins are a family of growth factors that act on neuronal cells. The neurotrophins include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3, -4 and -5. The action of neurotrophins depends on two transmembrane-receptor signalling systems: (1) the tropomyosin-related kinase (Trk) family of tyrosine kinase receptors (Trk A, Trk B and Trk C) and (2) the p75 neurotrophin receptor (p75(NTR)). The interaction between neurotrophic factors and their receptors may be involved in the mechanisms that regulate the differential susceptibility of neuronal populations in neurodegenerative diseases. The aim of the present study was to evaluate the role of neurotrophins in the pathogenesis of bovine spongiform encephalopathy (BSE) using a transgenic mouse overexpressing bovine prnp (BoTg 110). Histochemistry for Lycopersicum esculentum agglutinin, haematoxylin and eosin staining and immunohistochemistry for the abnormal isoform of the prion protein (PrP(d)), glial fibrillary acidic protein (GFAP), NGF, BDNF, NT-3 and the receptors Trk A, Trk B, Trk C and p75(NTR) was performed. The lesions and the immunolabelling patterns were assessed semiquantitatively in different areas of the brain. No significant differences in the immunolabelling of neurotrophins and their receptors were observed between BSE-inoculated and control animals, except for p75(NTR), which showed increased expression correlating with the distribution of lesions, PrP(d) deposition and gliosis in the BSE-inoculated mice. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Spontaneous obesity-linked type 2 diabetes in the absence of islet amyloid in a cynomolgus monkey infected with bovine spongiform encephalopathy.

    PubMed

    Strom, A; Yutzy, B; Kruip, C; Völker, I; Schloot, N C; Roden, M; Scott, F W; Löwer, J; Holznagel, E

    2013-09-01

    A 9-year-old cynomolgus monkey (Macaca fascicularis) infected orally with bovine spongiform encephalopathy (BSE) was presented for necropsy following euthanasia 4 years post infection (p.i.). This macaque R984 was exposed to a BSE dose that causes a simian form of variant Creutzfeldt-Jakob disease (vCJD) within 5 years p.i. in other macaques. All orally BSE-infected macaques developed a significant weight gain within the first 2 years p.i. compared with non-BSE-infected age- and sex-matched control animals, suggesting increased risk of type 2 diabetes (T2D). In contrast, macaque R984 developed rapid weight loss, hyperglycemia, and glucosuria and had to be euthanatized 4 years p.i. before clinical signs of vCJD. Pancreas histopathological evaluation revealed severe islet degeneration but, remarkably, no islet amyloid deposits were present. Immunostaining of pancreas sections for insulin and glucagon confirmed the loss of endocrine cells. In addition, prions were present in the adenohypophysis but not in other areas of the brain, indicating centripetal prion spread from the gut during the preclinical phase of BSE infection. Plasma glucose and insulin concentrations of macaque R984 became abnormal with age and resembled T2D. This unusual case of spontaneous T2D in the absence of islet amyloid deposits could have been due to early prion spread from the periphery to the endocrine system or could have occurred spontaneously.

  4. Detection and partial discrimination of atypical and classical bovine spongiform encephalopathies in cattle and primates using real-time quaking-induced conversion assay

    PubMed Central

    Levavasseur, Etienne; Biacabe, Anne-Gaëlle; Comoy, Emmanuel; Culeux, Audrey; Grznarova, Katarina; Privat, Nicolas; Simoneau, Steve; Flan, Benoit; Sazdovitch, Véronique; Seilhean, Danielle; Baron, Thierry; Haïk, Stéphane

    2017-01-01

    The transmission of classical bovine spongiform encephalopathy (C-BSE) through contaminated meat product consumption is responsible for variant Creutzfeldt-Jakob disease (vCJD) in humans. More recent and atypical forms of BSE (L-BSE and H-BSE) have been identified in cattle since the C-BSE epidemic. Their low incidence and advanced age of onset are compatible with a sporadic origin, as are most cases of Creutzfeldt-Jakob disease (CJD) in humans. Transmissions studies in primates and transgenic mice expressing a human prion protein (PrP) indicated that atypical forms of BSE may be associated with a higher zoonotic potential than classical BSE, and require particular attention for public health. Recently, methods designed to amplify misfolded forms of PrP have emerged as promising tools to detect prion strains and to study their diversity. Here, we validated real-time quaking-induced conversion assay for the discrimination of atypical and classical BSE strains using a large series of bovine samples encompassing all the atypical BSE cases detected by the French Centre of Reference during 10 years of exhaustive active surveillance. We obtained a 100% sensitivity and specificity for atypical BSE detection. In addition, the assay was able to discriminate atypical and classical BSE in non-human primates, and also sporadic CJD and vCJD in humans. The RT-QuIC assay appears as a practical means for a reliable detection of atypical BSE strains in a homologous or heterologous PrP context. PMID:28231300

  5. Effect of Q211 and K222 PRNP Polymorphic Variants in the Susceptibility of Goats to Oral Infection With Goat Bovine Spongiform Encephalopathy.

    PubMed

    Aguilar-Calvo, Patricia; Fast, Christine; Tauscher, Kerstin; Espinosa, Juan-Carlos; Groschup, Martin H; Nadeem, Muhammad; Goldmann, Wilfred; Langeveld, Jan; Bossers, Alex; Andreoletti, Olivier; Torres, Juan-María

    2015-08-15

    The prion protein-encoding gene (PRNP) is one of the major determinants for scrapie occurrence in sheep and goats. However, its effect on bovine spongiform encephalopathy (BSE) transmission to goats is not clear. Goats harboring wild-type, R/Q211 or Q/K222 PRNP genotypes were orally inoculated with a goat-BSE isolate to assess their relative susceptibility to BSE infection. Goats were killed at different time points during the incubation period and after the onset of clinical signs, and their brains as well as several peripheral tissues were analyzed for the accumulation of pathological prion protein (PrP(Sc)) and prion infectivity by mouse bioassay. R/Q211 goats displayed delayed clinical signs compared with wild-type goats. Deposits of PrP(Sc) were detected only in brain, whereas infectivity was present in peripheral tissues too. In contrast, none of the Q/K222 goats showed any evidence of clinical prion disease. No PrP(Sc) accumulation was observed in their brains or peripheral tissues, but very low infectivity was detected in some tissues very long after inoculation (44-45 months). These results demonstrate that transmission of goat BSE is genotype dependent, and they highlight the pivotal protective effect of the K222 PRNP variant in the oral susceptibility of goats to BSE. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Hepacivirus NS3/4A Proteases Interfere with MAVS Signaling in both Their Cognate Animal Hosts and Humans: Implications for Zoonotic Transmission.

    PubMed

    Anggakusuma; Brown, Richard J P; Banda, Dominic H; Todt, Daniel; Vieyres, Gabrielle; Steinmann, Eike; Pietschmann, Thomas

    2016-12-01

    Multiple novel members of the genus Hepacivirus have recently been discovered in diverse mammalian species. However, to date, their replication mechanisms and zoonotic potential have not been explored in detail. The NS3/4A serine protease of hepatitis C virus (HCV) is critical for cleavage of the viral polyprotein. It also cleaves the cellular innate immune adaptor MAVS, thus decreasing interferon (IFN) production and contributing to HCV persistence in the human host. To investigate the conservation of fundamental aspects of the hepaciviral life cycle, we explored if MAVS cleavage and suppression of innate immune signaling represent a common mechanism employed across different clades of the genus Hepacivirus to enhance viral replication. To estimate the zoonotic potential of these nonhuman hepaciviruses, we assessed if their NS3/4A proteases were capable of cleaving human MAVS. NS3/4A proteases of viruses infecting colobus monkeys, rodents, horses, and cows cleaved the MAVS proteins of their cognate hosts and interfered with the ability of MAVS to induce the IFN-β promoter. All NS3/4A proteases from nonhuman viruses readily cleaved human MAVS. Thus, NS3/4A-dependent cleavage of MAVS is a conserved replication strategy across multiple clades within the genus Hepacivirus Human MAVS is susceptible to cleavage by these nonhuman viral proteases, indicating that it does not pose a barrier for zoonotic transmission of these viruses to humans.

  7. Impact of climate change and man-made irrigation systems on the transmission risk, long-term trend and seasonality of human and animal fascioliasis in Pakistan.

    PubMed

    Afshan, Kiran; Fortes-Lima, Cesar A; Artigas, Patricio; Valero, Adela M; Qayyum, Mazhar; Mas-Coma, Santiago

    2014-05-01

    Large areas of the province of Punjab, Pakistan are endemic for fascioliasis, resulting in high economic losses due to livestock infection but also affecting humans directly. The prevalence in livestock varies pronouncedly in space and time (1-70%). Climatic factors influencing fascioliasis presence and potential spread were analysed based on data from five meteorological stations during 1990-2010. Variables such as wet days (Mt), water-budget-based system (Wb-bs) indices and the normalized difference vegetation index (NDVI), were obtained and correlated with geographical distribution, seasonality patterns and the two-decade evolution of fascioliasis in livestock throughout the province. The combined approach by these three indices proved to furnish a useful tool to analyse the complex epidemiology that includes (i) sheep-goats and cattlebuffaloes presenting different immunological responses to fasciolids; (ii) overlap of Fasciola hepatica and F. gigantica; (iii) co-existence of highlands and lowlands in the area studied; and (iv) disease transmission following bi-seasonality with one peak related to natural rainfall and another peak related to man-made irrigation. Results suggest a human infection situation of concern and illustrate how climate and anthropogenic environment modifications influence both geographical distribution and seasonality of fascioliasis risks. Increased fascioliasis risk throughout the Punjab plain and its decrease in the northern highlands of the province became evident during the study period. The high risk in the lowlands is worrying given that Punjab province largely consists of low-altitude, highly irrigated plains. The importance of livestock in this province makes it essential to prioritise adequate control measures. An annual treatment scheme to control the disease is recommended to be applied throughout the whole province.

  8. A case of spongiform polioencephalomyelopathy in a cat with a history of behavioural problems

    PubMed Central

    de la Fuente, Cristian; Pumarola, Martí; Amat, Marta; Le Brech, Susana; Manteca, Xavier

    2015-01-01

    A 7-month-old, entire female, domestic shorthair cat was referred to our behavioural service owing to soiling in the house and a play-related problem. The owners’ complaints were that the cat had never used the litter tray, and it did not know how to play. After reviewing the behavioural history, a problem of substrate preferences acquisition was suspected with regard to the elimination problem. During the consultation, the physical examination was unremarkable, but the neurological examination revealed a moderate and hypermetric ataxic gait, and a bilateral lack of menace response. Some degree of visual impairment was suspected. The problem was located in the central nervous system (CNS); specifically, an intracranial and multifocal problem was diagnosed. After a complete work-up (complete ophthalmological examination, complete blood count and a complete biochemistry panel, feline immunodeficiency virus/feline leukaemia virus test, thorax radiographs, abdominal ultrasound, brain magnetic resonance imaging [0.2 T], cerebrospinal fluid analysis and a urinary metabolic screen test), a degenerative CNS problem was suspected. No treatment was prescribed for the neurological problem. Regarding the problem of soiling in the house, reward-based training with a clicker was used, and the cat partially improved in a few weeks. Three months later, the cat was referred to the neurology service in status epilepticus. A symptomatic treatment was prescribed, with a mild response. After 2 years of treatment and a progressive worsening, the cat was euthanased. Necropsy revealed spongiform polioencephalomyelopathy. In order to rule out prion aetiology a PrPsc inmunohistochemistry assay was performed, and the results were negative. Congenital spongiform polioencephalomyelopathy (CSP) was diagnosed. We strongly suggest that the cat’s behavioural clinical signs were caused by the CSP, causing learning impairment. To the best of our knowledge, this would be the first case in which a

  9. Virus quantitation by transmission electron microscopy, TCID₅₀, and the role of timing virus harvesting: a case study of three animal viruses.

    PubMed

    Malenovska, Hana

    2013-08-01

    Quantitation of viruses is practised widely in both basic and applied virology. Infectious titration in cell cultures, the most common approach to it, is quite labour-intensive and alternative protocols are therefore sought. One of the alternatives is transmission electron microscope (TEM) quantitation using latex particles at a known concentration as a reference for counting virus particles. If virus TCID₅₀ is determined in parallel, the ratio of infectious to non-infectious virus particles may be established. This study employs such an approach to compute the number of virus particles and TCID₅₀, and establish their correlation for three viruses: Canine adenovirus 1 (CAdV-1), Feline calicivirus (FCV) and Bovine herpesvirus 1 (BoHV-1). Each of the viruses was grown in five replicates until complete cytopathology was recorded (time 0), then frozen. They were thawed, filter-sterilised and left for additional periods of 16, 32 and 48 h at 37°C. At each time point, the infectious ability of the virus was characterised by TCID50 and the number of virions quantified by TEM, in order to evaluate the influence of timing on virus harvest. The virus particle count determined by TEM did not change for any of the viruses throughout the experiment. The relationship between virus particle counts with TCID₅₀ at time 0 showed good linearity response; their ratio was almost constant. The virus particle-to-TCID₅₀ ratio varied between 146 and 426 (mean±SD: 282±103) for CAdV-1, between 36 and 79 (57±18) for FCV and between 110 and 249 (167±53) for BoHV-1. The proportion of non-infectious particles did not change throughout the experiment for either CAdV-1 or BoHV-1. However, a decrease in virus infectious ability disclosed by TCID₅₀ indicated that the fraction of non-infectious particles in FCV increased 300,000 times when time 0 and 48 h were compared. The quantitation of viruses with TEM is a simple and rapid protocol for virus quantitation but account must

  10. In vitro amplification of H-type atypical bovine spongiform encephalopathy by protein misfolding cyclic amplification

    PubMed Central

    O‘Connor, Matthew J.; Bishop, Keith; Workman, Robert G.; Maddison, Ben C.

    2017-01-01

    ABSTRACT The in vitro amplification of prions by serial protein misfolding cyclic amplification has been shown to detect PrPSc to levels at least as sensitive as rodent bioassay but in a fraction of the time. Bovine spongiform encephalopathy is a zoonotic prion disease in cattle and has been shown to occur in 3 distinct forms, classical BSE (C-BSE) and 2 atypical BSE forms (L-BSE and H-BSE). Atypical forms are usually detected in asymptomatic, older cattle and are suggested to be spontaneous forms of the disease. Here, we show the development of a serial protein misfolding cyclic amplification method for the detection of H-BSE. The assay could detect PrPSc from 3 distinct experimental isolates of H-BSE, could detect PrPSc in as little as 1×10−12 g of brain material and was highly specific. Additionally, the product of serial protein misfolding cyclic amplification at all dilutions of seed analyzed could be readily distinguished from L-BSE, which did not amplify, and C-BSE, which had PrPSc with distinct protease K-resistance and protease K-resistant PrPSc molecular weights. PMID:28281929

  11. The evolution of risk perceptions related to bovine spongiform encephalopathy--Canadian consumer and producer behavior.

    PubMed

    Yang, Jun; Goddard, Ellen

    2011-01-01

    In this study the dynamics of risk perceptions related to bovine spongiform encephalopathy (BSE) held by Canadian consumers and cow-calf producers were evaluated. Since the first domestic case of BSE in 2003, Canadian consumers and cow-calf producers have needed to make decisions on whether or not their purchasing/production behavior should change. Such changes in their behavior may relate to their levels of risk perceptions about BSE, risk perceptions that may be evolving over time and be affected by BSE media information available. An econometric analysis of the behavior of consumers and cow-calf producers might identify the impacts of evolving BSE risk perceptions. Risk perceptions related to BSE are evaluated through observed market behavior, an approach that differs from traditional stated preference approaches to eliciting risk perceptions at a particular point in time. BSE risk perceptions may be specified following a Social Amplification of Risk Framework (SARF) derived from sociology, psychology, and economics. Based on the SARF, various quality and quantity indices related to BSE media information are used as explanatory variables in risk perception equations. Risk perceptions are approximated using a predictive difference approach as defined by Liu et al. (1998). Results showed that Canadian consumer and cow-calf producer risk perceptions related to BSE have been amplified or attenuated by both quantity and quality of BSE media information. Government policies on risk communications need to address the different roles of BSE information in Canadian consumers' and cow-calf producers' behavior.

  12. Autoantibody to glial fibrillary acidic protein in the sera of cattle with bovine spongiform encephalopathy.

    PubMed

    Nomura, Sachiko; Miyasho, Taku; Maeda, Naoyuki; Doh-ura, Katsumi; Yokota, Hiroshi

    2009-08-01

    It is desirable to make the diagnosis in live cattle with bovine spongiform encephalopathy (BSE), and thus surrogate markers for the disease have been eagerly sought. Serum proteins from BSE cattle were analyzed by 2-D Western blotting and TOF-MS. Autoantibodies against proteins in cytoskeletal fractions prepared from normal bovine brains were found in the sera of BSE cattle. The protein recognized was identified to be glial fibrillary acidic protein (GFAP), which is expressed mainly in astrocytes in the brain. The antigen protein, GFAP, was also found in the sera of BSE cattle. The percentages of both positive sera in the autoantibody and GFAP were 44.0% for the BSE cattle, 0% for the healthy cattle, and 5.0% for the clinically suspected BSE-negative cattle. A significant relationship between the presence of GFAP and the expression of its autoantibody in the serum was recognized in the BSE cattle. These findings suggest a leakage of GFAP into the peripheral blood during neurodegeneration associated with BSE, accompanied by the autoantibody production, and might be useful in understanding the pathogenesis and in developing a serological diagnosis of BSE in live cattle.

  13. The Canadian Management of Bovine Spongiform Encephalopathy in Historical and Scientific Perspective, 1990-2014.

    PubMed

    Quimby, Alexandra E; Shamy, Michel C F

    2015-11-01

    On February 11, 2015, the Canadian Food Inspection Agency announced that a cow born and raised in Alberta had tested positive for bovine spongiform encephalopathy (BSE), commonly known as mad cow disease. BSE is a prion disease of cattle that, when transmitted to humans, produces a fatal neurodegenerative disease known as variant Creutzfeldt-Jakob disease. We believe that this latest case of BSE in Canadian cattle suggests the timeliness of a review of the management of BSE in Canada from a historically and scientifically informed perspective. In this article, we ask: how did the Canadian management of BSE between 1990 and 2014 engage with the contemporary understanding of BSE's human health implications? We propose that Canadian policies largely ignored the implicit medical nature of BSE, treating it as a purely agricultural and veterinary issue. In this way, policies to protect Canadians were often delayed and incomplete, in a manner disturbingly reminiscent of Britain's failed management of BSE. Despite assurances to the contrary, it is premature to conclude that BSE (and with it the risk of variant Creutzfeldt-Jakob disease) is a thing of Canada's past: BSE remains very much an issue in Canada's present.

  14. Brain-Specific Superoxide Dismutase 2 Deficiency Causes Perinatal Death with Spongiform Encephalopathy in Mice.

    PubMed

    Izuo, Naotaka; Nojiri, Hidetoshi; Uchiyama, Satoshi; Noda, Yoshihiro; Kawakami, Satoru; Kojima, Shuji; Sasaki, Toru; Shirasawa, Takuji; Shimizu, Takahiko

    2015-01-01

    Oxidative stress is believed to greatly contribute to the pathogenesis of various diseases, including neurodegeneration. Impairment of mitochondrial energy production and increased mitochondrial oxidative damage are considered early pathological events that lead to neurodegeneration. Manganese superoxide dismutase (Mn-SOD, SOD2) is a mitochondrial antioxidant enzyme that converts toxic superoxide to hydrogen peroxide. To investigate the pathological role of mitochondrial oxidative stress in the central nervous system, we generated brain-specific SOD2-deficient mice (B-Sod2(-/-)) using nestin-Cre-loxp system. B-Sod2(-/-) showed perinatal death, along with severe growth retardation. Interestingly, these mice exhibited spongiform neurodegeneration in motor cortex, hippocampus, and brainstem, accompanied by gliosis. In addition, the mutant mice had markedly decreased mitochondrial complex II activity, but not complex I or IV, in the brain based on enzyme histochemistry. Furthermore, brain lipid peroxidation was significantly increased in the B-Sod2(-/-), without any compensatory alterations of the activities of other antioxidative enzymes, such as catalase or glutathione peroxidase. These results suggest that SOD2 protects the neural system from oxidative stress in the perinatal stage and is essential for infant survival and central neural function in mice.

  15. Sulfated dextrans enhance in vitro amplification of bovine spongiform encephalopathy PrP(Sc) and enable ultrasensitive detection of bovine PrP(Sc).

    PubMed

    Murayama, Yuichi; Yoshioka, Miyako; Masujin, Kentaro; Okada, Hiroyuki; Iwamaru, Yoshifumi; Imamura, Morikazu; Matsuura, Yuichi; Fukuda, Shigeo; Onoe, Sadao; Yokoyama, Takashi; Mohri, Shirou

    2010-10-04

    Prions, infectious agents associated with prion diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep and goats, are primarily comprised of PrP(Sc), a protease-resistant misfolded isoform of the cellular prion protein PrP(C). Protein misfolding cyclic amplification (PMCA) is a highly sensitive technique used to detect minute amounts of scrapie PrP(Sc). However, the current PMCA technique has been unsuccessful in achieving good amplification in cattle. The detailed distribution of PrP(Sc) in BSE-affected cattle therefore remains unknown. We report here that PrP(Sc) derived from BSE-affected cattle can be amplified ultra-efficiently by PMCA in the presence of sulfated dextran compounds. This method is capable of amplifying very small amounts of PrP(Sc) from the saliva, palatine tonsils, lymph nodes, ileocecal region, and muscular tissues of BSE-affected cattle. Individual differences in the distribution of PrP(Sc) in spleen and cerebrospinal fluid samples were observed in terminal-stage animals. However, the presence of PrP(Sc) in blood was not substantiated in the BSE-affected cattle examined. The distribution of PrP(Sc) is not restricted to the nervous system and can spread to peripheral tissues in the terminal disease stage. The finding that PrP(Sc) could be amplified in the saliva of an asymptomatic animal suggests a potential usefulness of this technique for BSE diagnosis. This highly sensitive method also has other practical applications, including safety evaluation or safety assurance of products and byproducts manufactured from bovine source materials.

  16. Sulfated Dextrans Enhance In Vitro Amplification of Bovine Spongiform Encephalopathy PrPSc and Enable Ultrasensitive Detection of Bovine PrPSc

    PubMed Central

    Murayama, Yuichi; Yoshioka, Miyako; Masujin, Kentaro; Okada, Hiroyuki; Iwamaru, Yoshifumi; Imamura, Morikazu; Matsuura, Yuichi; Fukuda, Shigeo; Onoe, Sadao; Yokoyama, Takashi; Mohri, Shirou

    2010-01-01

    Background Prions, infectious agents associated with prion diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep and goats, are primarily comprised of PrPSc, a protease-resistant misfolded isoform of the cellular prion protein PrPC. Protein misfolding cyclic amplification (PMCA) is a highly sensitive technique used to detect minute amounts of scrapie PrPSc. However, the current PMCA technique has been unsuccessful in achieving good amplification in cattle. The detailed distribution of PrPSc in BSE-affected cattle therefore remains unknown. Methodology/Principal Findings We report here that PrPSc derived from BSE-affected cattle can be amplified ultra-efficiently by PMCA in the presence of sulfated dextran compounds. This method is capable of amplifying very small amounts of PrPSc from the saliva, palatine tonsils, lymph nodes, ileocecal region, and muscular tissues of BSE-affected cattle. Individual differences in the distribution of PrPSc in spleen and cerebrospinal fluid samples were observed in terminal-stage animals. However, the presence of PrPSc in blood was not substantiated in the BSE-affected cattle examined. Conclusions/Significance The distribution of PrPSc is not restricted to the nervous system and can spread to peripheral tissues in the terminal disease stage. The finding that PrPSc could be amplified in the saliva of an asymptomatic animal suggests a potential usefulness of this technique for BSE diagnosis. This highly sensitive method also has other practical applications, including safety evaluation or safety assurance of products and byproducts manufactured from bovine source materials. PMID:20957174

  17. Immunohistochemical characteristics of disease-associated PrP are not altered by host genotype or route of inoculation following infection of sheep with bovine spongiform encephalopathy.

    PubMed

    Martin, Stuart; González, Lorenzo; Chong, Angela; Houston, Fiona E; Hunter, Nora; Jeffrey, Martin

    2005-03-01

    It has previously been reported that disease-associated prion protein (PrP(d)) derived from natural scrapie and from sheep infected experimentally with bovine spongiform encephalopathy (BSE) differed in respect of their immunohistochemical and immunoblotting properties. For BSE, however, these initial observations were restricted to orally challenged sheep of the ARQ/ARQ PrP genotype. Here, extended examinations were performed on 28 sheep that developed neurological signs after BSE experimental infection by one of three routes. Intracerebrally infected ARQ/ARQ sheep showed more widespread and abundant accumulations of PrP(d) in tissues of the lymphoreticular system (LRS) than VRQ/VRQ animals, whereas no peripheral PrP(d) was detected in ARR/ARR sheep. The intensity and dissemination of PrP(d) accumulation in LRS tissues were less than those found previously in orally dosed sheep. AHQ/AHQ sheep challenged orally and ARQ/AHQ and ARQ/ARQ animals infected intravenously showed similar LRS-tissue PrP(d) distributions and levels to those of ARQ/ARQ sheep infected intracerebrally. The patterns of intra- and extracellular immunoreactivity to different PrP antibodies in brain and LRS tissues and the immunoblotting characteristics of PrP(res) from brain samples remained constant, irrespective of the route of inoculation and the PrP genotype, and were the same as described previously for ARQ/ARQ sheep dosed orally with BSE. These results suggest that the intracellular truncation of BSE PrP(d) and the proteinase K cleavage site of BSE PrP(res) are not altered by PrP genotype or by route of inoculation and that, therefore, screening tests based on these properties can be applied to identify potential sheep BSE cases occurring naturally.

  18. Human prion diseases: surgical lessons learned from iatrogenic prion transmission

    PubMed Central

    Bonda, David J.; Manjila, Sunil; Mehndiratta, Prachi; Khan, Fahd; Miller, Benjamin R.; Onwuzulike, Kaine; Puoti, Gianfranco; Cohen, Mark L.; Schonberger, Lawrence B.; Cali, Ignazio

    2016-01-01

    The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood “infectious protein” has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial

  19. Detection of bovine meat and bone meal in animal feed at a level of 0.1%.

    PubMed

    Aarts, Henk J M; Bouw, El M; Buntjer, Jaap B; Lenstra, Johannes A; Van Raamsdonk, Leo W D

    2006-01-01

    For the control of the transmission of bovine spongiform encephalopathy in cattle via feedstuff, a real-time polymerase chain reaction assay was developed with ruminant-specific Bov-B SINE primers, SYBR Green fluorescence detection, and melting curve analysis. In formulated cattle and chicken feed samples spiked with pure bovine and sheep meat and bone meal heated at 133 degrees C for 20 min, a contamination level of 0.1% was detected.

  20. Airborne transmission of Bordetella pertussis.

    PubMed

    Warfel, Jason M; Beren, Joel; Merkel, Tod J

    2012-09-15

    Pertussis is a contagious, acute respiratory illness caused by the bacterial pathogen Bordetella pertussis. Although it is widely believed that transmission of B. pertussis occurs via aerosolized respiratory droplets, no controlled study has ever documented airborne transmission of pertussis. We set out to determine if airborne transmission occurs between infected and naive animals, utilizing the baboon model of pertussis. Our results showed that 100% of exposed naive animals became infected even when physical contact was prevented, demonstrating that pertussis transmission occurs via aerosolized respiratory droplets.

  1. Foodborne-Transmitted Prions From the Brain of Cows With Bovine Spongiform Encephalopathy Ascend in Afferent Neurons to the Simian Central Nervous System and Spread to Tonsils and Spleen at a Late Stage of the Incubation Period.

    PubMed

    Holznagel, Edgar; Yutzy, Barbara; Kruip, Carina; Bierke, Par; Schulz-Schaeffer, Walter; Löwer, Johannes

    2015-11-01

    Protease-resistant prion protein (PrP(res)) accumulation in lymphoreticular tissues indicates prion infection. To date, tonsillectomy and appendectomy samples have been used in population prevalence surveys to detect clinically silent carriers of variant Creutzfeldt-Jakob disease (vCJD). However, the temporal sequence of prion spread in the human body is still not known. We therefore traced the temporal-spatial pattern of PrP(res) accumulation in the body of a simian vCJD model. Cynomolgus monkeys were fed brain of (eleven) cows with bovine spongiform encephalopathy, and some were euthanized before and some after onset of neurological signs. PrP(res) was detected in tissues by a paraffin-embedded tissue blot technique and a semiquantitative Western immunoblot assay. Bovine spongiform encephalopathy (BSE)-associated prions were preferentially transported from the gut to the central nervous system (CNS) along sensory nerve fibers and initially entered the simian CNS at lumbar spinal cord levels. In asymptomatic animals, we found BSE in 50% and 12% of gut- and tonsil-derived samples, respectively. Unlike in rodents and ruminants, foodborne BSE-associated prions entered the simian CNS via afferent neurons. From sites of initial CNS invasion, prions spread centrifugally to tonsils and spleen at an advanced stage of the incubation period, thus explaining why tonsil specimens were not reliable for detection of simian disease carriers before onset of clinical signs. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Contaminants in feed for food-producing animals.

    PubMed

    Moreno-López, J

    2002-01-01

    Outbreaks of Bovine Spongiform Encephalopathy (BSE) and food borne microbial infections, dioxin contaminated animal products, the presence of veterinary drug residues, microbial resistance to antibiotics, mycotoxins, agricultural and industrial chemicals, etc. are serious concerns for the food industry in many countries. Since the direct links between feed safety and safety of foods of animal origin are obvious, feed production and manufacture should be considered as an integral part of the food production chain. Industry is responsible for the quality and safety of food and feed that is produced. This paper is a brief review of some microorganisms as source of infections for farm animals that could result in human illnesses. These include Salmonella enterica, Bacillus anthracis, Toxoplasma gondii, Trichinella spiralis, prions, Listeria monocytogenes, EHEC, Campylobacter, Clostridium botulinum, Hog Cholera virus, Foot and Mouth Disease virus, etc. as well as other contaminants associated with animal feed such as mycotoxins, veterinary drugs, dioxins and PCB and Genetically Modified Organisms.

  3. Consumer reactions to risk information on bovine spongiform encephalopathy in Japan

    PubMed Central

    Yasunaga, Hideo; Obana, Naoya; Ogawa, Toshio; Imamura, Tomoaki

    2010-01-01

    Objectives To investigate the impact of information on foodborne disease on consumers, we quantified consumers’ anxiety, purchasing behaviors, and willingness-to-pay (WTP) in response to the reading of newspaper articles published in 2001 that documented the first cow in Japan to be infected with bovine spongiform encephalopathy (BSE). Methods An online questionnaire survey of 993 females aged 20–59 years was conducted in 2007. The participants were randomly selected from the general population via the Internet and were divided into three groups. Each group was assigned a different number of BSE-related articles to read, namely, two, four, and six articles, respectively. Each participant described her personal level of anxiety, underlying reasons for her anxiety, and changes in purchasing behavior after reading the articles. The respondents who wanted to buy guaranteed-safe beef were asked to state their maximal WTP. Results The level of anxiety was significantly lower and distrust of the relevant administration significantly greater in the group asked to read six articles than in the other groups. The WTP value for guaranteed beef was approximately 1.3-fold higher than the regular purchase price, with significant differences between groups. In the ‘six-article’ group, the ratio between WTP and the regular purchase price was significantly less than that in the ‘four-article’ group. Conclusions These findings suggest that the anxiety of consumers can be reduced if they receive an appropriate amount of published information. WTP may be linked to the contents of the articles. PMID:21432560

  4. Quantitative analysis of wet-heat inactivation in bovine spongiform encephalopathy

    SciTech Connect

    Matsuura, Yuichi; Ishikawa, Yukiko; Bo, Xiao; Murayama, Yuichi; Yokoyama, Takashi; Somerville, Robert A.; Kitamoto, Tetsuyuki; Mohri, Shirou

    2013-03-01

    Highlights: ► We quantitatively analyzed wet-heat inactivation of the BSE agent. ► Infectivity of the BSE macerate did not survive 155 °C wet-heat treatment. ► Once the sample was dehydrated, infectivity was observed even at 170 °C. ► A quantitative PMCA assay was used to evaluate the degree of BSE inactivation. - Abstract: The bovine spongiform encephalopathy (BSE) agent is resistant to conventional microbial inactivation procedures and thus threatens the safety of cattle products and by-products. To obtain information necessary to assess BSE inactivation, we performed quantitative analysis of wet-heat inactivation of infectivity in BSE-infected cattle spinal cords. Using a highly sensitive bioassay, we found that infectivity in BSE cattle macerates fell with increase in temperatures from 133 °C to 150 °C and was not detected in the samples subjected to temperatures above 155 °C. In dry cattle tissues, infectivity was detected even at 170 °C. Thus, BSE infectivity reduces with increase in wet-heat temperatures but is less affected when tissues are dehydrated prior to the wet-heat treatment. The results of the quantitative protein misfolding cyclic amplification assay also demonstrated that the level of the protease-resistant prion protein fell below the bioassay detection limit by wet-heat at 155 °C and higher and could help assess BSE inactivation. Our results show that BSE infectivity is strongly resistant to wet-heat inactivation and that it is necessary to pay attention to BSE decontamination in recycled cattle by-products.

  5. Immunohistochemical distinction between preclinical bovine spongiform encephalopathy and scrapie infection in sheep.

    PubMed

    Thuring, C M A; van Keulen, L J M; Langeveld, J P M; Vromans, M E W; van Zijderveld, F G; Sweeney, T

    2005-01-01

    Sheep are susceptible experimentally to bovine spongiform encephalopathy (BSE), the clinical signs being indistinguishable from those of scrapie. Because of the possibility of natural ovine BSE infection, laboratory tests are needed to distinguish between scrapie and BSE infection. The objectives of this study were to determine whether (1) PrPSc accumulates in biopsy samples of the tonsil or third eyelid, or both, of BSE-infected sheep before the appearance of clinical disease, and (2) such samples from BSE- and scrapie-infected sheep differ in respect of PrPSc accumulations. Homozygous ARQ sheep (n = 10) were dosed orally at 4-5 months of age with a brain homogenate from BSE-infected cattle. Third eyelid and tonsillar biopsy samples were taken at < or = 6 monthly intervals post-infection and examined immunohistochemically for PrPSc. Third eyelid protuberances were difficult to identify, resulting in many unsuitable samples; however, third eyelid samples shown to contain lymphoid follicles were invariably negative for PrPSc. In contrast, tonsillar biopsy samples became positive for PrPSc from 11 to 20 months post-infection. Consistent differences in the morphology of PrPSc granules in tingible body macrophages (TBMs) between BSE- and scrapie-infected sheep were detected with anti-peptide antibodies directed towards amino acids 93-106 of the ovine prion protein: thus, PrPSc appeared as single granules in TBMs of tonsillar sections from BSE-infected sheep, whereas clusters of PrPSc granules were observed within TBMs in the tonsils of scrapie-infected sheep. In contrast, antibodies against epitopes situated N- and C-terminally from the 93-106 region of the ovine prion protein revealed no differences between BSE- and scrapie-infected sheep in terms of PrPSc granules in TBMs.

  6. Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey.

    PubMed

    Gill, O Noel; Spencer, Yvonne; Richard-Loendt, Angela; Kelly, Carole; Dabaghian, Reza; Boyes, Lynnette; Linehan, Jacqueline; Simmons, Marion; Webb, Paul; Bellerby, Peter; Andrews, Nick; Hilton, David A; Ironside, James W; Beck, Jon; Poulter, Mark; Mead, Simon; Brandner, Sebastian

    2013-10-15

    To carry out a further survey of archived appendix samples to understand better the differences between existing estimates of the prevalence of subclinical infection with prions after the bovine spongiform encephalopathy epizootic and to see whether a broader birth cohort was affected, and to understand better the implications for the management of blood and blood products and for the handling of surgical instruments. Irreversibly unlinked and anonymised large scale survey of archived appendix samples. Archived appendix samples from the pathology departments of 41 UK hospitals participating in the earlier survey, and additional hospitals in regions with lower levels of participation in that survey. 32,441 archived appendix samples fixed in formalin and embedded in paraffin and tested for the presence of abnormal prion protein (PrP). Of the 32,441 appendix samples 16 were positive for abnormal PrP, indicating an overall prevalence of 493 per million population (95% confidence interval 282 to 801 per million). The prevalence in those born in 1941-60 (733 per million, 269 to 1596 per million) did not differ significantly from those born between 1961 and 1985 (412 per million, 198 to 758 per million) and was similar in both sexes and across the three broad geographical areas sampled. Genetic testing of the positive specimens for the genotype at PRNP codon 129 revealed a high proportion that were valine homozygous compared with the frequency in the normal population, and in stark contrast with confirmed clinical cases of vCJD, all of which were methionine homozygous at PRNP codon 129. This study corroborates previous studies and suggests a high prevalence of infection with abnormal PrP, indicating vCJD carrier status in the population compared with the 177 vCJD cases to date. These findings have important implications for the management of blood and blood products and for the handling of surgical instruments.

  7. Epidemics of emerging animal diseases and food-borne infection problems over the last 5 years in Japan.

    PubMed

    Yamane, Itsuro

    2006-10-01

    There have been several emerging animal diseases and food-borne infection problems occurring in Japan over the last 5 years. We describe brief pictures of these epidemics and our control activities. As acute contagious and/or emerging animal diseases, the foot and mouth disease (FMD) outbreak caused by the Pan-Asian topotype of the type O virus occurred in March 2000 after 92 years of FMD-free status. In 2004, four cases of the highly pathogenic avian influenza (HPAI), which was the first outbreak after 79 years, and caused by the H5N1 subtype, were identified. As part of the responses against these outbreaks, all the animals in the affected farms were destroyed, and movement control areas were established around the infected premises, and a nation-wide intensive survey for FMD and HPAI was performed. As for food-borne or feed-borne infections, the first bovine spongiform encephalopathy (BSE) was identified in September 2001 and 19 more cases have been reported until June 2005. A large outbreak of food-borne infection caused by low-fat milk contaminated with enterotoxin A produced by Staphylococcus aureus, involving more than 13,000 patients, occurred in 2000. In 2003, people who consumed uncooked liver and meat from wild boar and deer developed clinical signs of hepatitis caused by the hepatitis E virus. Pork is also suspected as natural source of virus transmission. Early detection of the first cases and rapid action in preventing and controlling the spread of infections are very important combined with proper risk communication about correct information of the diseases.

  8. [Oral transmission of Chagas' disease].

    PubMed

    Toso M, Alberto; Vial U, Felipe; Galanti, Norbel

    2011-02-01

    The traditional transmission pathways of Chagas' disease are vectorial, transfusional, transplacental and organ transplantation. However, oral transmission is gaining importance. The first evidence of oral transmission was reported in Brazil in 1965. Nowadays the oral route is the transmission mode in 50% of cases in the Amazon river zone. Oral infection is produced by the ingestion of infected triatomine bugs or their feces, undercooked meat from infested host animals and food contaminated with urine or anal secretion of infected marsupials. Therefore travelers to those zones should be advised about care to be taken with ingested food. In Chile, this new mode of transmission should be considered in public health policies.

  9. Universal white blood cell reduction in Europe: has transmission of variant Creutzfeldt-Jakob disease been prevented?

    PubMed

    Vamvakas, Eleftherios C

    2011-04-01

    Universal white blood cell (WBC) reduction was introduced in Europe to prevent transmission of variant Creutzfeldt-Jakob disease (vCJD) by transfusion. Findings from rodent models indicate that WBC reduction should not prevent vCJD transmission because the residual plasma infectivity suffices to infect transfusion recipients even under optimistic infectivity assumptions. Although infectivity in human blood may not partition in the manner in which it is distributed in rodents, prion-reduction filters remove the residual plasma infectivity in rodent models. Precautionary introduction of prion filtration in the UK--for patients without dietary exposure to bovine spongiform encephalopathy and in the absence of a reported case of vCJD transmission attributable to infectivity residing in plasma--is consistent with the (already in place for such subjects) precautionary importation to the UK of fresh frozen plasma from low-risk countries. Thus, implementation of prion filtration in the UK does not imply that universal WBC reduction--as currently practiced in Europe--does not abrogate transmission of vCJD. Because neither a human case of vCJD transmission through transfusion of WBC-reduced red blood cells nor a case of experimental bovine spongiform encephalopathy transmission by WBC-reduced transfusion to sheep has been reported, it cannot be concluded that ordinary WBC reduction is ineffective in preventing transfusion transmission in humans. Accordingly, universal WBC reduction for the prevention of vCJD in Europe should continue.

  10. Aerosol Transmission of Filoviruses.

    PubMed

    Mekibib, Berhanu; Ariën, Kevin K

    2016-05-23

    Filoviruses have become a worldwide public health concern because of their potential for introductions into non-endemic countries through international travel and the international transport of infected animals or animal products. Since it was first identified in 1976, in the Democratic Republic of Congo (formerly Zaire) and Sudan, the 2013-2015 western African Ebola virus disease (EVD) outbreak is the largest, both by number of cases and geographical extension, and deadliest, recorded so far in medical history. The source of ebolaviruses for human index case(s) in most outbreaks is presumptively associated with handling of bush meat or contact with fruit bats. Transmission among humans occurs easily when a person comes in contact with contaminated body fluids of patients, but our understanding of other transmission routes is still fragmentary. This review deals with the controversial issue of aerosol transmission of filoviruses.

  11. Aerosol Transmission of Filoviruses

    PubMed Central

    Mekibib, Berhanu; Ariën, Kevin K.

    2016-01-01

    Filoviruses have become a worldwide public health concern because of their potential for introductions into non-endemic countries through international travel and the international transport of infected animals or animal products. Since it was first identified in 1976, in the Democratic Republic of Congo (formerly Zaire) and Sudan, the 2013–2015 western African Ebola virus disease (EVD) outbreak is the largest, both by number of cases and geographical extension, and deadliest, recorded so far in medical history. The source of ebolaviruses for human index case(s) in most outbreaks is presumptively associated with handling of bush meat or contact with fruit bats. Transmission among humans occurs easily when a person comes in contact with contaminated body fluids of patients, but our understanding of other transmission routes is still fragmentary. This review deals with the controversial issue of aerosol transmission of filoviruses. PMID:27223296

  12. A comparative study of modified confirmatory techniques and additional immuno-based methods for non-conclusive autolytic bovine spongiform encephalopathy cases.

    PubMed

    Sarasa, Rocío; Becher, Dietmar; Badiola, Juan J; Monzón, Marta

    2013-10-18

    In the framework of the Bovine Spongiform Encephalopathy (BSE) surveillance programme, samples with non-conclusive results using the OIE confirmatory techniques have been repeatedly found. It is therefore necessary to question the adequacy of the previously established consequences of this non-conclusive result: the danger of failing to detect potentially infected cattle or erroneous information that may affect the decision of culling or not of an entire bovine cohort. Moreover, there is a very real risk that the underreporting of cases may possibly lead to distortion of the BSE epidemiological information for a given country.In this study, samples from bovine nervous tissue presenting non-conclusive results by conventional OIE techniques (Western blot and immunohistochemistry) were analyzed. Their common characteristic was a very advanced degree of autolysis. All techniques recommended by the OIE for BSE diagnosis were applied on all these samples in order to provide a comparative study. Specifically, immunohistochemistry, Western blotting, SAF detection by electron microscopy and mouse bioassay were compared. Besides, other non confirmatory techniques, confocal scanning microscopy and colloidal gold labelling of fibrils, were applied on these samples for confirming and improving the results. Immunocytochemistry showed immunostaining in agreement with the positive results finally provided by the other confirmatory techniques. These results corroborated the suitability of this technique which was previously developed to examine autolysed (liquified) brain samples. Transmission after inoculation of a transgenic murine model TgbovXV was successful in all inocula but not in all mice, perhaps due to the very scarce PrPsc concentration present in samples.Electron microscopy, currently fallen into disuse, was demonstrated to be, not only capable to provide a final diagnosis despite the autolytic state of samples, but also to be a sensitive diagnostic alternative for

  13. Highly Efficient Prion Transmission by Blood Transfusion

    PubMed Central

    Andréoletti, Olivier; Litaise, Claire; Simmons, Hugh; Corbière, Fabien; Lugan, Séverine; Costes, Pierrette; Schelcher, François; Vilette, Didier; Grassi, Jacques; Lacroux, Caroline

    2012-01-01

    It is now clearly established that the transfusion of blood from variant CJD (v-CJD) infected individuals can transmit the disease. Since the number of asymptomatic infected donors remains unresolved, inter-individual v-CJD transmission through blood and blood derived products is a major public health concern. Current risk assessments for transmission of v-CJD by blood and blood derived products by transfusion rely on infectious titers measured in rodent models of Transmissible Spongiform Encephalopathies (TSE) using intra-cerebral (IC) inoculation of blood components. To address the biological relevance of this approach, we compared the efficiency of TSE transmission by blood and blood components when administrated either through transfusion in sheep or by intra-cerebral inoculation (IC) in transgenic mice (tg338) over-expressing ovine PrP. Transfusion of 200 µL of blood from asymptomatic infected donor sheep transmitted prion disease with 100% efficiency thereby displaying greater virulence than the transfusion of 200 mL of normal blood spiked with brain homogenate material containing 103ID50 as measured by intracerebral inoculation of tg338 mice (ID50 IC in tg338). This was consistent with a whole blood titer greater than 103.6 ID50 IC in tg338 per mL. However, when the same blood samples were assayed by IC inoculation into tg338 the infectious titers were less than 32 ID per mL. Whereas the transfusion of crude plasma to sheep transmitted the disease with limited efficacy, White Blood Cells (WBC) displayed a similar ability to whole blood to infect recipients. Strikingly, fixation of WBC with paraformaldehyde did not affect the infectivity titer as measured in tg338 but dramatically impaired disease transmission by transfusion in sheep. These results demonstrate that TSE transmission by blood transfusion can be highly efficient and that this efficiency is more dependent on the viability of transfused cells than the level of infectivity measured by IC

  14. Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

    PubMed Central

    2011-01-01

    Atypical bovine spongiform encephalopathy (BSE) has recently been identified in Europe, North America, and Japan. It is classified as H-type and L-type BSE according to the molecular mass of the disease-associated prion protein (PrPSc). To investigate the topographical distribution and deposition patterns of immunolabeled PrPSc, H-type BSE isolate was inoculated intracerebrally into cattle. H-type BSE was successfully transmitted to 3 calves, with incubation periods between 500 and 600 days. Moderate to severe spongiform changes were detected in the cerebral and cerebellar cortices, basal ganglia, thalamus, and brainstem. H-type BSE was characterized by the presence of PrP-immunopositive amyloid plaques in the white matter of the cerebrum, basal ganglia, and thalamus. Moreover, intraglial-type immunolabeled PrPSc was prominent throughout the brain. Stellate-type immunolabeled PrPSc was conspicuous in the gray matter of the cerebral cortex, basal ganglia, and thalamus, but not in the brainstem. In addition, PrPSc accumulation was detected in the peripheral nervous tissues, such as trigeminal ganglia, dorsal root ganglia, optic nerve, retina, and ne