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inhibitors of gastric acid secretion increase the risk of prion infection in mice.gastric juice is a unique combination of hydrochloric acid and the proteolytic enzyme pepsin. its main function is to inactivate ingested microorganisms. prions cause fatal transmissible degenerative encephalopathies in animals and man. these diseases have attracted attention due to the proposed link between bovine spongiform encephalopathy in cattle and the occurrence of a new variant creutzfeldt-jakob disease in humans where the most probable route of transmission is via contaminated food. the ...201121936725
squirrel monkeys (saimiri sciureus) infected with the agent of bovine spongiform encephalopathy develop tau pathology.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 t ...201122018806
comparison of nanofiltration efficacy in reducing infectivity of centrifuged versus ultracentrifuged 263k scrapie-infected brain homogenates in "spiked" albumin solutions.background: the safety of plasma-derived products is of concern for possible transmission of variant creutzfeldt-jakob disease. the absence of validated screening tests requires the use of procedures to remove or inactivate prions during the manufacture of plasma-derived products to minimize the risk of transmission. these procedures need proper validation studies based on spiking human plasma or intermediate fractions of plasma fractionation with prions in a form as close as possible to that pr ...201122082124
consumers' understanding and concerns about bovine spongiform encephalopathy (bse): comparison among canadian, american, and japanese consumers.in spite of much analysis of the impact of bovine spongiform encephalopathy (bse) on consumer perceptions and meat purchases, there has been little explicit analysis of the level of bse knowledge. in this study the role of knowledge about bse was examined in canada, the united states, and japan. in addition, the level of knowledge was linked to human health concerns regarding bse and whether there is agreement with paying a premium for beef with bse animal tests. from a public policy perspective ...201122043916
Comparison of candidate vCJD in vitro diagnostic assays using identical sample sets.Background and Objectives With four transfusion related transmissions of variant Creutzfeldt-Jakob Disease (vCJD), three of which developed clinical disease and the other died of other causes but was positive for markers of infection, there is an increased urgency to identify and implement a test for blood donor screening. With limited amounts of blood samples from vCJD cases available test evaluation is challenging. Alternative approaches are therefore needed. Control and vCJD tissues homogena ...201122126309
risk of prion disease transmission through bovine-derived bone substitutes: a systematic review.background: despite the causal association between variant creutzfeldt - jakob disease and bovine spongiform encephalopathy (bse), bovine origin graft materials are widely used during dental surgical procedures. the aim of this study was to assess the risk of bse transmission through anorganic bovine bone substitutes. methods: electronic database of medline was searched to identify relevant studies regarding our focused questions, presence of bse prion infectivity in raw bovine bone, bse prion i ...201122171533
The Management of Blood Safety in the Presence of Uncertain Risk: A United Kingdom Perspective.Millions of patients in the UK benefit from the use of both plasma derivatives and blood components that are seen as critical interventions in current medicine. Measures are in place to significantly reduce the risks associated with blood transfusion and plasma derivatives; however, these measures themselves are not risk free. Over the past 20 years, advances in technology and regulation have seen major reductions in the risks associated with transfusion. International blood services, industry, ...201122126710
The structural stability of wild-type horse prion protein.Prion diseases (e.g. Creutzfeldt-Jakob disease (CJD), variant CJD (vCJD), Gerstmann-Straussler-Scheinker syndrome (GSS), Fatal Familial Insomnia (FFI) and Kuru in humans, scrapie in sheep, bovine spongiform encephalopathy (BSE or 'mad-cow' disease) and chronic wasting disease (CWD) in cattles) are invariably fatal and highly infectious neurodegenerative diseases affecting humans and animals. However, by now there have not been some effective therapeutic approaches or medications to treat all the ...201121875155
transcriptional modulation in a leukocyte-depleted splenic cell population during prion disease.prion replication in the periphery precedes neuroinvasion in many experimental rodent scrapie models, and in natural sheep scrapie and chronic wasting disease (cwd) in cervids. prions propagate in the germinal centers of secondary lymphoid organs and are strongly associated with follicular dendritic cells (fdc) and possibly circulating dendritic cells and macrophages. given the importance of lymphoid organs in prion disease transmission and pathogenesis, gene expression studies may reveal host f ...201122043911
The molecular epidemiology of variant CJD.The emergence of the novel prion diseases bovine spongiform encephalopathy (BSE) and, subsequently, variant Creutzfeldt-Jakob disease (vCJD) in epidemic forms has attracted much scientific attention. The oral transmission of these disorders, the causative relationship of vCJD to BSE and the resistance of the transmissible agents in both disorders to conventional forms of decontamination has caused great public health concern. The size of the still emerging vCJD epidemic is thankfully much lower ...201121915360
notification and support for people exposed to the risk of creutzfeldt-jakob disease (cjd) (or other prion diseases) through medical treatment (iatrogenically).creutzfeldt-jakob disease (cjd) and variant cjd (vcjd) are rare and always-fatal diseases transmissible via certain medical procedures. if a person is exposed to the disease risk through medical treatment, they may need to be notified of this to prevent them passing the risk to others in healthcare settings and to enable additional infection control measures to be put in place for certain procedures. as cjd is incurable, and unable to be screened for or effectively treated, communicating this ri ...201121412905
the first report of a patient with probable variant creutzfeldt-jakob disease in turkey.variant creutzfeldt-jakob disease (vcjd) was first reported in the uk in 1996. here, we report the first turkish case of vcjd. a 47-year-old man, who has never lived outside of turkey and had had no transfusion, was admitted to the university hospital with speech disorder, cognitive decline and ataxia following depression, irritability, and personality change. the immunoassay of the 14-3-3 protein in the cerebrospinal fluid was negative. brain magnetic resonance imaging revealed high-signal lesi ...201122279448
variant creutzfeldt-jakob disease in the united kingdom: a countrywide or local risk?the aim of this study was to identify factors that may have augmented local risks for variant creutzfeldt-jakob disease (vcjd).201019692715
a quantitative study of the pathological changes in the cortical white matter in variant creutzfeldt-jakob disease (vcjd).to quantify cortical white matter pathology in variant creutzfeldt-jakob disease (vcjd) and to correlate white and grey matter pathologies.201021073844
phase i/ii safety study of transfusion of prion-filtered red cell concentrates in transfusion-dependent patients.variant creutzfeldt-jakob (vcjd) is a fatal transfusion transmissible prion infection. no test for vcjd in the donor population is currently available. therefore, prion removal by filtration of red cell concentrate (rcc) is an attractive option for prevention.201020345513
feasibility study of a screening assay that identifies the abnormal prion protein prptse in plasma: initial results with 20,000 samples.it is likely that transmission of variant creutzfeldt-jakob disease (vcjd) occurs by transfusion and that the candidate infectious agent (prp(tse)) is present in small concentrations in the blood of infected donors in the asymptomatic phase of the disease. a new blood screening assay has been developed to detect prp(tse) in citrated plasma samples.201020088835
variant creutzfeldt-jakob disease: the first confirmed case from portugal shows early onset, long duration and unusual pathology.we present clinical and autopsy findings in the first case of variant creutzfeldt-jakob disease diagnosed and confirmed in portugal. onset was at 11 years, the earliest onset reported, and the course (32 months) relatively long. western blot showed protease resistant prion protein, mainly of type 4 (2b) isoform. the cerebral cortex revealed severe spongiform change with numerous amyloid plaques, which did not fit the definition of florid plaques. in the striatum, spongiform change was limited bu ...201020019229
the epidemiology of progressive intellectual and neurological deterioration in childhood.to study the epidemiology of diseases that cause progressive intellectual and neurological deterioration (pind) in uk children.201019948513
differences in the density and spatial distribution of florid and diffuse plaques in variant creutzfeldt-jakob disease (vcjd).to determine whether in cases of variant creutzfeldt-jakob disease (vcjd), the florid-type plaques are derived from the diffuse plaques or whether the 2 plaque types develop independently.201014531544
detection of blood-transmissible agents: can screening be miniaturized?transfusion safety relating to blood-transmissible agents is a major public health concern, particularly when faced with the continuing emergence of new infectious agents. these include new viruses appearing alongside other known reemerging viruses (west nile virus, chikungunya) as well as new strains of bacteria and parasites (plasmodium falciparum, trypanosoma cruzi) and finally pathologic prion protein (variant creutzfeldt-jakob disease). genomic mutations of known viruses (hepatitis b virus, ...201020546202
a highly sensitive immunoassay for the detection of prion-infected material in whole human blood without the use of proteinase k.the causal association of variant creutzfeldt-jakob disease (vcjd) with bovine spongiform encephalopathy has raised significant concerns for public health. assays for vcjd infection are vital for the application of therapeutics, for the screening of organ donations, and to maintain a safe blood supply. currently the best diagnostic tools for vcjd depend upon the detection of disease-associated prion protein (prp(sc) ), which is distinguished from normal background prp (prp(c) ) by proteinase k ( ...201020561299
photo essay. mri and positron emission tomography findings in heidenhain variant creutzfeldt-jakob disease.the typical presentation of heidenhain variant creutzfeldt-jakob disease (cjd) is a rapidly progressive visual loss in the setting of a relatively normal ophthalmologic examination. at presentation, patients with this uniformly fatal illness frequently demonstrate only minor cortical abnormalities on mri. here, we document the clinical presentation and imaging results of a patient with heidenhain variant cjd in whom abnormalities on positron emission tomographic imaging were more evident than ch ...201020581692
variant creutzfeldt-jakob disease.summary: variant creutzfeldt-jakob disease (cjd) is an emerging form of human prion disease caused by oral exposure to the bovine spongiform encephalopathy agent. most cases have occurred in the uk, but smaller numbers of cases have been identified in 10 other countries worldwide. all confirmed cases belong to a single genetic subgroup defined by methionine homozygosity at codon 129 in the prion protein gene. variant cjd has a widespread distribution of infectivity in the body, involving lymphoi ...201020590878
sex effect in mouse and human prion disease.sex effect on the incubation period of variant creutzfeldt-jakob disease (vcjd) disease in human and me-7 murine models was investigated. in the 167 vcjd cases reported in the united kingdom as of january 2009, age at onset was significantly lower in female patients (by 2 years) than in male patients after stratification on birth cohort. in c57/bl6n mice infected with me-7 scrapie strain, incubation was shorter in female than in male mice. the incubation period increased in castrated male mice a ...201020594106
prion interaction with the 37-kda/67-kda laminin receptor on enterocytes as a cellular model for intestinal uptake of prions.enterocytes, a major cell population of the intestinal epithelium, represent one possible barrier to the entry of prions after oral exposure. we established a cell culture system employing enterocytes from different species to study alimentary prion interaction with the 37-kda/67-kda laminin receptor lrp/lr. human, bovine, porcine, ovine, and cervid enterocytes were cocultured with brain homogenates from cervid, sheep, and cattle suffering from chronic wasting disease (cwd), scrapie, and bovine ...201020603132
heterozygosity at polymorphic codon 219 in variant creutzfeldt-jakob disease.genetic variants of the prion protein gene (prnp) strongly determine susceptibility to prion diseases. all tested patients with definite variant creutzfeldt-jakob disease (vcjd) are homozygous for methionine at a common polymorphism at codon 129. a further genetic polymorphism at codon 219, a common variant in several asian populations, is considered protective against sporadic cjd.201020697057
human prion diseases in the united states.prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. the most common form of human prion disease, creutzfeldt-jakob disease (cjd), occurs worldwide. variant cjd (vcjd), a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy. this study describes the occurrence and epidemiology of cjd and vcjd in the united states.201020049325
variant cjd infection in the spleen of a neurologically asymptomatic uk adult patient with haemophilia.summary: all uk patients with bleeding disorders treated with any uk-sourced pooled factor concentrates between 1980 and 2001 have been informed that they may be at an increased risk of infection with variant creutzfeldt-jakob disease (vcjd). we describe a study to detect disease-associated, protease-resistant prion protein (prp(res)) in 17 neurologically aymptomatic patients with haemophilia considered to be at increased risk of vcjd. materials from 11 autopsy and seven biopsy cases were analys ...201020070383
scotblood 2009: the quest for understanding vcjd; claudia's trachea implantation; transfusion triggers; scottish histocompatibility and immunogenetics network; and islet cell transplantation.scotblood 2009 consisted of a varied combination of leading edge presentations incorporating the past, present and future. variant cjd was a major feature of the meeting comprising the quest for its understanding and the impact the disease was having on blood donation. the meeting also included the fascinating and groundbreaking story of claudia's trachea transplantation, along with progress in the establishment of the scottish histocompatibility and immunogenetics network and islet transplantat ...201020089457
multiorgan detection and characterization of protease-resistant prion protein in a case of variant cjd examined in the united states.variant creutzfeldt-jakob disease (vcjd) is a prion disease thought to be acquired by the consumption of prion-contaminated beef products. to date, over 200 cases have been identified around the world, but mainly in the united kingdom. three cases have been identified in the united states; however, these subjects were likely exposed to prion infection elsewhere. here we report on the first of these subjects.201020098730
a single step multiplex immunofluorometric assay for differential diagnosis of bse and scrapie.although there is no evidence that the european sheep population has been infected with bovine spongiform encephalopathy (bse), distinguishing this from scrapie is paramount, given the association between bse exposure and the human transmissible spongiform encephalopathy (tse), variant creutzfeldt-jakob disease. the capability to differentially diagnose tses in sheep is thus essential in order to safeguard the food chain and human health. biochemical methods for differentiating bse and scrapie a ...201020214905
increasing hybridoma viability and antibody repertoire after the cell fusion by the use of human plasma as an alternative supplement.prion diseases such as bovine spongiform encephalopathy (bse) and new variant creutzfeldt-jakob disease (nvcjd) have caused a major safety concern in cell cultures using fetal calf serum (fcs). in this study, we found that screened and tested human plasma (hp) obtained from blood centers may be an ideal alternate nutrient substitute to fcs for culturing hybridoma. in addition to the inherent safety, a ten-fold increase in the fusion efficiency has been observed if the hp was used as the nutrient ...201020723546
prospective 10-year surveillance of human prion diseases in japan.we analysed the epidemiological data and clinical features of patients with prion diseases that had been registered by the creutzfeldt-jakob disease surveillance committee, japan, over the past 10 years, since 1999. we obtained information on 1685 japanese patients suspected as having prion diseases and judged that 1222 patients had prion diseases, consisting of definite (n=180, 14.7%) and probable (n=1029, 84.2%) cases, except for dura mater graft-associated creutzfeldt-jakob disease which also ...201020855418
the relative safety of pooled whole-blood-derived platelets prepared by the buffy-coat method versus single-donor (apheresis) platelets.conversion to a single-donor (apheresis) platelet inventory in western europe and other countries that provide similar health care to the us but rely on buffy-coat pooled whole-blood-derived platelets will confer the benefit of a > or = 2-fold reduction in the risk of all emerging transfusion-transmitted infections (ttis). in europe, this benefit will include a > or = 2-fold reduction in the risk of acquiring variant creutzfeldt-jakob disease (vcjd) from platelet transfusion. in countries that u ...201020857891
review: contribution of transgenic models to understanding human prion disease.transgenic mice expressing human prion protein in the absence of endogenous mouse prion protein faithfully replicate human prions. these models reproduce all of the key features of human disease, including long clinically silent incubation periods prior to fatal neurodegeneration with neuropathological phenotypes that mirror human prion strain diversity. critical contributions to our understanding of human prion disease pathogenesis and aetiology have only been possible through the use of transg ...201020880036
magnetization transfer ratio may be a surrogate of spongiform change in human prion diseases.human prion diseases are fatal neurodegenerative disorders caused by misfolding of the prion protein. there are no useful biomarkers of disease progression. cerebral cortex spongiform change, one of the classical pathological features of prion disease, resolves in prion-infected transgenic mice following prion protein gene knockout. we investigated the cross-sectional, longitudinal and post-mortem cerebral magnetization transfer ratios as a surrogate for prion disease pathology. twenty-three pri ...201020881162
large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in britain.there have been 173 cases of variant creutzfeldt-jakob disease (vcjd) in the uk, as of 5 july 2010, as a result of the bovine spongiform encephalopathy epidemic. the number of individuals subclinically infected with vcjd, and thus the eventual number of cases, remains, however, uncertain. in an attempt to address this problem, 63,007 tonsil tissue specimens were previously tested by enzyme immunoassay (eia) for the presence of disease-related prion protein (prp(res)) and found to be negative. to ...201020922767
dispersion of prion protein deposits around blood vessels in variant creutzfeldt-jakob disease.in variant creutzfeldt-jakob disease (vcjd), a disease linked to bovine spongiform encephalopathy (bse), florid-type prion protein (prp(sc)) deposits are aggregated around the larger diameter (> 10 µm) cerebral microvessels. clustering of prp(sc) deposits around blood vessels may result from blood-borne prions or be a consequence of the cerebral vasculature influencing the development of the florid deposits. to clarify the factors involved, the dispersion of the florid prp(sc) deposits was studi ...201020924999
[anaesthetic management for caesarean delivery and creutzfeldt-jakob disease].variant creutzfeldt-jakob disease (vcjd) is the only form of prion diseases linked to bovine spongiform encephalopathy (bse). the surgical and anaesthetic management in patients having creutzfeldt-jakob disease is rare. maternofoetal and human transmission of creutzfeldt-jakob disease is still unknown. the principles for managing these new risks are not described in obstetric recommendations. we report the case of an 18-year-old woman, who developed the variant creutzfeldt-jakob disease during h ...201020934303
the prion diseases.the prion diseases are a family of rare neurodegenerative disorders that result from the accumulation of a misfolded isoform of the prion protein (prp), a normal constituent of the neuronal membrane. five subtypes constitute the known human prion diseases; kuru, creutzfeldt-jakob disease (cjd), gerstmann-sträussler-scheinker syndrome (gss), fatal insomnia (fi), and variant cjd (vcjd). these subtypes are distinguished, in part, by their clinical phenotype, but primarily by their associated brain ...201020938044
differentiation of ruminant transmissible spongiform encephalopathy isolate types, including bovine spongiform encephalopathy and ch1641 scrapie.with increased awareness of the diversity of transmissible spongiform encephalopathy (tse) strains in the ruminant population, comes an appreciation of the need for improved methods of differential diagnosis. exposure to bovine spongiform encephalopathy (bse) has been associated with the human tse, variant creutzfeldt-jakob disease, emphasizing the necessity in distinguishing low-risk tse types from bse. tse type discrimination in ruminants such as cattle, sheep, goats and deer, requires the app ...201020943889
correlation of polydispersed prion protein and characteristic pathology in the thalamus in variant creutzfeldt-jakob disease: implication of small oligomeric species.the vacuolation, neuronal loss and gliosis that characterize human prion disease pathology are accompanied by the accumulation of an aggregated, insoluble and protease-resistant form (termed prp(sc)) of the host-encoded normal cellular prion protein (prp(c)). in variant creutzfeldt-jakob disease the frontal cortex and cerebellum exhibit intense vacuolation and the accumulation of prp(sc) in the form of amyloid plaques and plaque-like structures. in contrast the posterior thalamus is characterize ...201021029243
underestimation of the expression of cellular prion protein on human red blood cells.recent transmissions of variant creutzfeldt-jakob disease by blood transfusion emphasize the need for the development of prion screening tests. the detection of prions in blood is complicated by the presence of poorly characterized cellular prion protein (prp(c) ) in both plasma and blood cells. according to published studies, most of prp(c) in blood cells resides in platelets (plts) and white blood cells.201021058954
the risk of transmitting prion disease by blood or plasma products.various experimental studies have shown infectivity in blood in relation to bovine spongiform encephalitis (bse) and variant creutzfeldt-jakob disease (vcjd). human to human transmission vcjd infection has been reported via transfusion of non-leukocyte-reduced red cells and, probably, via factor viii concentrates. a number of precautionary measures are in place but uncertainties remain, especially concerning the number of bse-infected people in the population. additional measures such as prion f ...201021071277
a standardized comparison of commercially available prion decontamination reagents using the standard steel-binding assay.prions are comprised principally of aggregates of a misfolded host protein and cause fatal transmissible neurodegenerative disorders of mammals, such as variant creutzfeldt-jakob disease in humans and bovine spongiform encephalopathy in cattle. prions pose significant public health concerns through contamination of blood products and surgical instruments, and can resist conventional hospital sterilization methods. prion infectivity binds avidly to surgical steel and can efficiently transfer infe ...201021084494
preclinical deposition of pathological prion protein in muscle of experimentally infected primates.prion diseases are transmissible fatal neurodegenerative disorders affecting humans and animals. a central step in disease progression is the accumulation of a misfolded form (prp(sc)) of the host encoded prion protein (prp(c)) in neuronal and non-neuronal tissues. the involvement of peripheral tissues in preclinical states increases the risk of accidental transmission. on the other hand, detection of prp(sc) in non-neuronal easy-accessible compartments such as muscle may offer a novel diagnosti ...201021085647
atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control.since 1987, when bovine spongiform encephalopathy (bse) emerged as a novel disease in cattle, enormous efforts were undertaken to monitor and control the disease in ruminants worldwide. the driving force was its high economic impact, which resulted from trade restrictions and the loss of consumer confidence in beef products, the latter because bse turned out to be a fatal zoonosis, causing variant creutzfeldt-jakob disease in human beings. the ban on meat and bone meal in livestock feed and the ...201021088166
immunomodulation for prion and prion-related diseases.prion diseases are a unique category of illness, affecting both animals and humans, where the underlying pathogenesis is related to a conformational change of a normal self protein called cellular prion protein to a pathological and infectious conformer known as scrapie prion protein (prp(sc)). currently, all prion diseases lack effective treatment and are universally fatal. past experiences with bovine spongiform encephalopathy and variant creutzfeldt-jakob disease mainly in europe, as well as ...201021105779
the retinoic acid receptor beta (rarb) region of mmu14 is associated with prion disease incubation time in mouse.in neurodegenerative conditions such as alzheimer's and prion disease it has been shown that host genetic background can have a significant effect on susceptibility. indeed, human genome-wide association studies (gwas) have implicated several candidate genes. understanding such genetic susceptibility is relevant to risks of developing variant cjd (vcjd) in populations exposed to bovine spongiform encephalopathy (bse) and understanding mechanisms of neurodegeneration. in mice, aspects of prion di ...201021151910
probable variant creutzfeldt–jakob disease in asia: a case report from taiwan and review of two prior cases.new variant creutzfeldt–jakob disease (vcjd) was first identified in the uk in 1996, and was causally linked to bovine spongiform encephalopathy. herein we report the first case of vcjd in taiwan: a 34-year-old man who had lived in the uk between 1989 and 1997. the patient presented with depression, irritability, personality change, painful feet and allodynia, followed by gait ataxia and cognitive impairment. electroencephalograms did not show the typical appearance of sporadic cjd. the cerebros ...201021155168
uncertainty in the tail of the variant creutzfeldt-jakob disease epidemic in the uk.despite low case numbers the variant creutzfeldt-jakob disease epidemic poses many challenges for public health planning due to remaining uncertainties in disease biology and transmission routes. we develop a stochastic model for variant cjd transmission, taking into account the known transmission routes (food and red-cell transfusion) to assess the remaining uncertainty in the epidemic. we use bayesian methods to obtain scenarios consistent with current data. our results show a potentially long ...201021203419
laminar distribution of the pathological changes in sporadic and variant creutzfeldt-jakob disease.the laminar distributions of the pathological changes in the cerebral cortex were compared in the prion diseases sporadic creutzfeldt-jakob disease (scjd) and variant cjd (vcjd). first, in some cortical regions, the vacuolation ("spongiform change") was more generally distributed across the cortex in scjd. second, there was greater neuronal loss in the upper cortex in vcjd and in the lower cortex in scjd. third, the "diffuse" and "florid" prion protein (prp(sc)) deposits were more frequently dis ...201021209711
variant creutzfeldt-jakob disease in a transfusion recipient: coincidence or cause?to date there have been four instances of infection transmitted through blood transfusions derived from individuals who later developed variant creutzfeldt-jakob disease (vcjd). the identification of further transmission of vcjd through this route would have important implications for risk assessment and public health.201020230536
[variant creutzfeld-jakob disease (vcjd) : epidemiology and prevention from human to human secondary transmission].in the wake of the bovine spongiform encephalopathy (bse) epidemic, variant creutzfeldt-jakob disease (vcjd) has emerged as a previously unknown prion disease of humans. the initial occurrence of vcjd was observed in 1995/1996, and, so far, a total of 219 vcjd cases have been reported worldwide from seven european and four non-european countries. of these, 172 cases were observed in the united kingdom. the exact prevalence of sub- or pre-clinical vcjd infections is unclear. despite effective mea ...201020449549
[protection from bse : efforts, measures, success, and costs].by the mid 1980s, bovine spongiform encephalopathy (bse) emerged in the united kingdom (uk) and reached its peak in the early 1990s with up to 37,000 cases. in the year 2000, bse was diagnosed for the first time for a cow born in germany. since then, 413 cases of bse have been detected. about 10 years after the first bse cases were detected, variant creutzfeldt-jakob disease (vcjd), a new variant of creutzfeldt-jakob disease (cjd), was described in the uk. legal measures for protection from bse ...201020449555
risk reduction strategies for variant creutzfeldt-jakob disease transmission by uk plasma products and their impact on patients with inherited bleeding disorders.summary: the appearance and rapid evolution of bse in uk cattle in the mid 1980s, with compelling data supporting variant creutzfeldt-jakob disease (vcjd) as its human manifestation, pose a potentially severe threat to public health. three clinical cases and one asymptomatic case of vcjd infection have been reported in uk recipients of non-leucodepleted red cell transfusions from donors subsequently diagnosed with vcjd. plasma from both these and other donors who later developed vcjd has contrib ...201020487442
emerging pathogens in transfusion medicine.although the risk of infection with hepatitis and human immunodeficiency viruses from blood transfusions has been reduced to negligible levels, emerging infections continue to offer threats. such threats occur with any infection that has an asymptomatic, blood-borne phase. in the past, it was thought that any emerging transfusion-transmitted disease would have epidemiologic properties similar to those of aids or viral hepatitis. over the past 20 years, however, greatest concern has arisen from v ...201020513567
validation of diagnostic criteria for variant creutzfeldt-jakob disease.variant creutzfeldt-jakob disease (vcjd), a novel form of human prion disease, was recognized in 1996. the disease affected a younger cohort than sporadic cjd, and the early clinical course was dominated by psychiatric and sensory symptoms. in an attempt to aid diagnosis and establish standardization between surveillance networks, diagnostic criteria were established. these were devised from the features of a small number of cases and modified in 2000 as the clinical phenotype was established. s ...201020517937
pathological phenotype of sheep scrapie after blood transfusion.blood transfusion practices have resulted in iatrogenic cases of variant creutzfeldt-jakob disease (vcjd) and it is known that sheep blood is also infectious in the pre-clinical stages of natural scrapie and experimentally induced bovine spongiform encephalopathy (bse). further investigations have also shown that the pathological phenotype of sheep bse and human vcjd is maintained after blood transfusion. the present study describes the pathological phenotype, in terms of accumulation of the dis ...201019625026
quantitative measurement of the efficacy of protein removal by cleaning formulations; comparative evaluation of prion-directed cleaning chemistries.the stability of the infectious agent causing variant creutzfeldt-jakob disease (vcjd) has highlighted the importance of cleaning surgical instruments for controlling potential spread of iatrogenic cjd. in this study, thermostable adenylate kinases (taks) in test soil were coated on to stainless steel and these surrogate agents used to evaluate the efficacy of a range of cleaning chemistries in a bench-top washer disinfector (btwd), or as a pre-soak either with or without subsequent treatment by ...201019833409
increase in cd230 (cellular prion protein) fluorescence on blood lymphocytes in bovine spongiform encephalopathy-infected nonhuman primates.the cellular prion protein (prp(c)) plays a central role in prion diseases such as variant creutzfeldt-jakob disease. this disease can be transmitted by blood transfusion. however, the exact kinetics of blood infectivity and the blood fraction carrying infectivity have not yet been identified.201019843289
fast, broad-range disinfection of bacteria, fungi, viruses and prions.effective disinfectants are of key importance for the safe handling and reprocessing of surgical instruments. this study tested whether new formulations containing sds, naoh and 1-propanol (n-propanol) are simultaneously active against a broad range of pathogens including bacteria, fungi, non-enveloped viruses and prions. inactivation and disinfection were examined in suspension and on carriers, using coagulated blood or brain homogenate as an organic contaminant. coomassie blue staining was use ...201019864502
evaluation of removal of prion infectivity from red blood cells with prion reduction filters using a new rapid and highly sensitive cell culture-based infectivity assay.the clearance of infectious prions from biologic fluids is usually quantified by bioassays based on intracerebral inoculation of hamsters or mice; these tests are slow, cumbersome, imprecise, and very expensive. in the present study we describe the use of a new and highly sensitive cell culture-based infectivity assay to evaluate the performance of several prion removal prototype filters.201020003057
[prion disease surveillance in japan: analysis of 1,241 patients].the creutzfeldt-jakob disease (cjd) surveillance committee has identified 1,241 patients with prion diseases during 1999-2009, including 953 with sporadic cjd (scjd) (76.8%), 207 with genetic prion diseases (16.7%), 78 with environmentally acquired prion diseases (6.3%), and 3 with unclassified cjd. among atypical cases of scjd, most common was mm2 type including the cortical and thalamic forms. the genetic cases included 84 with a prp v180i mutation (40.6%), 37 with a p102l mutation (17.9%), 34 ...200920030254
prnp variation in uk sporadic and variant creutzfeldt jakob disease highlights genetic risk factors and a novel non-synonymous polymorphism.genetic analysis of the human prion protein gene (prnp) in suspect cases of creutzfeldt-jakob disease (cjd) is necessary for accurate diagnosis and case classification. previous publications on the genetic variation at the prnp locus have highlighted the presence of numerous polymorphisms, in addition to the well recognised one at codon 129, with significant variability between geographically distinct populations. it is therefore of interest to consider their influence on susceptibility or the c ...200920035629
age-related alterations affect the susceptibility of mice to prion infection.the sporadic and familial forms of creutzfeldt-jacob disease (scjd and fcjd) usually appear at older ages (60-70 years and approximately 50, respectively). nevertheless, infectious forms such as kuru and variant cjd (vcjd) present mostly at a much earlier age. to study the effect of age on the pathogenesis of infectious prion disease, we inoculated young and aged mice intraperitoneally with rml prions, followed them to disease end point and studied their disease characteristics. we now show that ...200920045218
age of onset and death in inherited prion disease are heritable.the common polymorphism at codon 129 of the prion protein gene (prnp) is known to affect prion disease susceptibility, incubation period and phenotype. mouse quantitative trait locus (qtl) studies demonstrate multiple modifiers of incubation time unlinked to prnp, suggesting the existence of homologous human prion disease modifiers, but direct evidence of these has been lacking. we investigated the correlation of age at onset and death, expressed as a composite z score, between parents and offsp ...200918729123
transmissions of variant creutzfeldt-jakob disease from brain and lymphoreticular tissue show uniform and conserved bovine spongiform encephalopathy-related phenotypic properties on primary and secondary passage in wild-type mice.prion strains are defined by their biological properties after transmission to wild-type mice, specifically by their incubation periods and patterns of vacuolar pathology ('lesion profiles'). preliminary results from transmissions of variant creutzfeldt-jakob disease (vcjd) to wild-type mice provided the first compelling evidence for the close similarity of the vcjd agent to the agent causing bovine spongiform encephalopathy (bse). complete results from this investigation, including the transmis ...200919656962
a traceback phenomenon can reveal the origin of prion infection.the transmission of prions to animals with incongruent prion protein (prp) gene (referred to as cross-sequence transmission) results in a relatively long incubation period and can generate a new prion strain with unique transmissibility designated as a traceback phenomenon. for example, cross-sequence transmission of bovine spongiform encephalopathy (bse) prions to human generated variant creutzfeldt-jakob disease (vcjd) prions which retained the transmissibility to mice expressing bovine prp. t ...200919659941
canadian media representations of mad cow disease.a canadian case of bovine spongiform encephalopathy (bse) or "mad cow disease" was confirmed in may, 2003. an in-depth content analysis of newspaper articles was conducted to understand the portrayal of bse and variant creutzfeldt-jakob disease (vcjd) in the canadian media. articles in the "first 10 days" following the initial discovery of a cow with bse in canada on may 20, 2003, were examined based on the premise that these initial stories provide the major frames that dominate news media repo ...200919697246
detection of prpsc in blood from sheep infected with the scrapie and bovine spongiform encephalopathy agents.the role of blood in the iatrogenic transmission of transmissible spongiform encephalopathy (tse) or prion disease has become an increasing concern since the reports of variant creutzfeldt-jakob disease (vcjd) transmission through blood transfusion from humans with subclinical infection. the development of highly sensitive rapid assays to screen for prion infection in blood is of high priority in order to facilitate the prevention of transmission via blood and blood products. in the present stud ...200919740979
high sensitivity detection of the glial fibrillary acidic protein as indicator for tse risk material in meat products using an immuno-pcr.the emergence of prion diseases in cattle during the bovine spongiform encephalopathy (bse) epidemic and the transmission to humans causing variant creutzfeldt-jakob disease by consume of bse-contaminated meat has focused attention on the use of tissues from the central nervous system (cns) in food. to avoid food contamination, it is regulated by law that specified risk material has to be removed from food chains. detection of well-expressed cns indicator proteins such as the glial fibrillary ac ...200919753609
repetitive immunization enhances the susceptibility of mice to peripherally administered prions.the susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. while little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. here we administered prions to mice that were repeatedly immunized by two initial injections of cpg oligodeoxynucleotides followed by repeated injections of bovine se ...200919779609
the effects of host age on follicular dendritic cell status dramatically impair scrapie agent neuroinvasion in aged mice.following peripheral exposure, many transmissible spongiform encephalopathy (tse) agents accumulate first in lymphoid tissues before spreading to the cns (termed neuroinvasion) where they cause neurodegeneration. early tse agent accumulation upon follicular dendritic cells (fdcs) in lymphoid follicles appears critical for efficient neuroinvasion. most clinical cases of variant creutzfeldt-jakob disease have occurred in young adults, although the reasons behind this apparent age-related susceptib ...200919786551
inter-laboratory assessment of prpsc typing in creutzfeldt-jakob disease: a western blot study within the neuroprion consortium.molecular typing is of considerable importance for the surveillance and epidemiology of human transmissible spongiform encephalopathies (tses). it relies on the detection of distinct protease-resistant prion protein (prp(sc)) core fragments that differ in molecular mass and/or glycoform ratio. in this collaborative study, we tested the inter-laboratory agreement in tse molecular typing. sixteen characterized brain specimens from sporadic tses and variant creutzfeldt-jakob disease (vcjd) cases we ...200918624793
prion proteins in subpopulations of white blood cells from patients with sporadic creutzfeldt-jakob disease.recent cases of prion transmission in humans following transfusions using blood donated by patients with asymptomatic variant creutzfeldt-jakob disease (cjd) implicate the presence of prion infectivity in peripheral blood. in this study, we examined the levels of the normal, cellular prion protein (prpc), and the disease-causing isoform (prpsc) in subpopulations of circulating white blood cells (wbcs) from patients with sporadic (s) cjd, age-matched neurological controls and healthy donors. thou ...200919434060
prevalence of disease related prion protein in anonymous tonsil specimens in britain: cross sectional opportunistic survey.to establish with improved accuracy the prevalence of disease related prion protein (prp(cjd)) in the population of britain and thereby guide a proportionate public health response to limit the threat of healthcare associated transmission of variant creutzfeldt-jakob disease (vcjd).200919460798
prion protein expression and processing in human mononuclear cells: the impact of the codon 129 prion gene polymorphism.so far, all clinical cases of new variant creutzfeldt-jakob disease (vcjd), thought to result from the bovine spongiform encephalopathy (bse) prion agent, have shown methionine-methionine (m/m) homozygosity at the m129v polymorphism of the prnp gene. although established, this relationship is still not understood. in both vcjd and experimental bse models prion agents do reach the bloodstream, raising concerns regarding disease transmission through blood transfusion.200919495414
two unusual bovine spongiform encephalopathy cases detected in great britain.bovine spongiform encephalopathy (bse) was first identified in great britain (gb) in 1986 and was subsequently detected in many other countries, worldwide. a decade after the start of the bovine epidemic, the first cases of new variant creutzfeldt-jakob disease (vcjd) in humans were linked to probable ingestion of bse infected tissue, highlighting a new zoonotic disease. an abnormal protease-resistant protein (prp(res)) in a diseased subject, derived from a post-translational change of a normal ...200919497088
shadoo (sprn) and prion disease incubation time in mice.prion diseases are transmissible neurodegenerative disorders of mammalian species and include scrapie, bovine spongiform encephalopathy (bse), and variant creutzfeldt-jakob disease (vcjd). the prion protein (prp) plays a key role in the disease, with coding polymorphism in both human and mouse influencing disease susceptibility and incubation time, respectively. other genes are also thought to be important and a plausible candidate is sprn, which encodes the prp-like protein shadoo (sho). sho is ...200919513788
antibody-based immunotherapeutic attempts in experimental animal models of prion diseases.there has been a dramatic decrease in the risk of transmission of bovine spongiform encephalopathy to humans. in contrast, the risk of human-to-human transmission of variant creutzfeldt-jakob disease (vcjd) via medical treatments became potentially high since 4 vcjd cases were reported to be possibly transmitted through blood transfusion in the uk. however, no treatments are yet available for curing prion diseases.200919514955
prion removal effect of a specific affinity ligand introduced into the manufacturing process of the pharmaceutical quality solvent/detergent (s/d)-treated plasma octaplaslg.a new chromatographic step for the selective binding of abnormal prion protein (prp(sc)) was developed, and optimization for prp(sc) capture was achieved by binding to an affinity ligand attached to synthetic resin particles. this step was implemented into the manufacturing process of the solvent/detergent (s/d)-treated biopharmaceutical quality plasma octaplas to further improve the safety margin in terms of risk for variant creutzfeldt-jakob disease (vcjd) transmission.200919548963
[risk factors for sporadic creutzfeldt-jakob disease].sporadic creutzfeldt-jakob disease (scjd) is the most common form of human transmissible spongiform encephalopathies (prion disease), but its cause has not been fully elucidated. according to its biochemical properties prion protein is resistant to routine sterilisation methods. thus, invasive medical procedures could be involved in the genesis of the disease. present knowledge about iatrogenic routes of transmission, oral infection and transmission via blood products in variant cjd (vcjd) under ...200919551608
inactivation of animal and human prions by hydrogen peroxide gas plasma sterilization.prions cause various transmissible spongiform encephalopathies. they are highly resistant to the chemical and physical decontamination and sterilization procedures routinely used in healthcare facilities. the decontamination procedures recommended for the inactivation of prions are often incompatible with the materials used in medical devices. in this study, we evaluated the use of low-temperature hydrogen peroxide gas plasma sterilization systems and other instrument-processing procedures for i ...200919563265
elimination capacity of a tse-model agent in the manufacturing process of alphanate/fanhdi, a human factor viii/vwf complex concentrate.the variant creutzfeldt-jakob disease (vcjd) is a transmissible spongiform encephalopathy (tse), mainly present in the uk and is associated with the ingestion of bovine products affected with bovine spongiform encephalopathy. manufacturers of biological products must investigate the ability of their production processes to remove tse agents. we studied the purification steps in the manufacturing process of two fviii/vwf concentrates (alphanate) and fanhdi in their ability to eliminate an experim ...200919563480
genomic and post-genomic analyses of human prion diseases.abstract : prion diseases share common features of neurodegenerative disorders, infectious diseases and pathologies linked to misfolded proteins. whether these aspects are independently and fortuitously present in prion diseases or are somewhat linked together remains unsettled, but the contribution of genomic, proteomic, metabolomic and spectroscopic techniques might give insights into this puzzle, and likely give hope for therapy to patients. although the prion protein gene (prnp) governs most ...200919566915
human variant creutzfeldt-jakob disease and sheep scrapie prp(res) detection using seeded conversion of recombinant prion protein.the pathological isoform of the prion protein (prp(res)) can serve as a marker for prion diseases, but more practical tests are needed for preclinical diagnosis and sensitive detection of many prion infections. previously we showed that the quaking-induced conversion (quic) assay can detect sub-femtogram levels of prp(res) in scrapie-infected hamster brain tissue and distinguish cerebral spinal fluid (csf) samples from normal and scrapie-infected hamsters. we now report the adaptation of the qui ...200919570812
reflections on a half-century in the field of transmissible spongiform encephalopathy.the subject of transmissible spongiform encephalopathy may properly be said to have begun with the experimental transmission of scrapie by cuillé and chelle in 1936, although creutzfeldt and jakob had described the disease that bears their names in 1920-21. thirty more years passed before the human disease was also shown to be transmissible, in 1966, and the following half century has seen the field move from classical biology to molecular biology and genetics, and from 'slow virus' to host-enco ...200919618333
kuru: its ramifications after fifty years.kuru was the first human neurodegenerative disease in the group of transmissible spongiform encephalopathies, prion diseases or, in the past, slow unconventional virus diseases. it was reported to western medicine in 1957 by gajdusek and zigas. kuru was spread by endocannibalism and because of this the ratio of affected women and children to men was excessive. the hallmark of kuru neuropathology is the amyloid plaque. we may speculate what would happen if kuru had not been discovered or did not ...200918606515
human platelets as a substrate source for the in vitro amplification of the abnormal prion protein (prp) associated with variant creutzfeldt-jakob disease.four recent cases of transfusion-related transmission of variant creutzfeldt-jakob disease (vcjd) highlight the need to develop a highly sensitive and specific screening test to detect infectivity in the blood of asymptomatic infected individuals. protein misfolding cyclic amplification (pmca), a method for the amplification of minute amounts of disease-associated abnormal prion protein (prp(sc)) to readily detectable levels, could be incorporated into such a test provided that a suitable substr ...200918980616
bacterial colitis increases susceptibility to oral prion disease.dietary exposure to prion-contaminated materials has caused kuru and variant creutzfeldt-jakob disease in humans and transmissible spongiform encephalopathies (tses) in cattle, mink, and felines. the epidemiology of dietary prion infections suggests that host genetic modifiers and possibly exogenous cofactors may play a decisive role in determining disease susceptibility. however, few cofactors influencing susceptibility to prion infection have been identified. in the present study, we investiga ...200919072552
human prion protein (prp) 219k is converted to prpsc but shows heterozygous inhibition in variant creutzfeldt-jakob disease infection.prion protein gene (prnp) e219k is a human polymorphism commonly occurring in asian populations but is rarely found in patients with sporadic creutzfeldt-jakob disease (cjd). thus the polymorphism e219k has been considered protective against sporadic cjd. the corresponding mouse prion protein (prp) polymorphism variant (mouse prp 218k) is not converted to the abnormal isoform (prp(sc)) and shows a dominant negative effect on wild-type prp conversion. to define the conversion activity of this hum ...200919074151
are further genetic factors associated with the risk of developing variant creutzfeldt-jakob disease? 200919081509
genetic risk factors for variant creutzfeldt-jakob disease: a genome-wide association study.human and animal prion diseases are under genetic control, but apart from prnp (the gene that encodes the prion protein), we understand little about human susceptibility to bovine spongiform encephalopathy (bse) prions, the causal agent of variant creutzfeldt-jakob disease (vcjd).200919081515
strain-specific viral properties of variant creutzfeldt-jakob disease (vcjd) are encoded by the agent and not by host prion protein.human cjd, endemic sheep scrapie, epidemic bovine spongiform encephalopathy (bse), and other transmissible spongiform encephalopathies (tses), are caused by a group of related but molecularly uncharacterized infectious agents. the uk-bse agent infected many species, including humans where it causes variant cjd (vcjd). as in most viral infections, different tse disease phenotypes are determined by both the agent strain and the host species. tse strains are most reliably classified by incubation t ...200919097123
production and characterization of a panel of monoclonal antibodies against native human cellular prion protein.the human prion diseases, such as variant creutzfeldt-jakob disease (vcjd), are characterized by the conversion of the normal cellular prion protein (prp(c)) into an abnormal disease associated form (prp(sc)). monoclonal antibodies (mabs) that recognize these different prp isoforms are valuable reagents both in the diagnosis of these diseases and in prion disease research in general but we know of no attempts to raise mabs against native human prp(c). we immunized prion protein gene ablated (prp ...200919132894
risk of creutzfeldt-jakob disease transmission by ocular surgery and tissue transplantation.creutzfeldt-jakob disease (cjd) is a rare, fatal neurodegenerative disease that occurs in sporadic, genetic, variant, and iatrogenic forms. the transformation of normal prion protein (prp(c)) to the abnormal form (prp(sc)) is a key step in the pathogenesis of cjd and leads to the accumulation of amyloid and spongiform changes in the brain. the presence of prp(sc) in tissue is a surrogate marker for cjd infectivity. sporadic cjd, whose cause is unknown, is by far the most frequent form with 1-2 c ...200919136921
from mad cows to sensible blood transfusion: the risk of prion transmission by labile blood components in the united kingdom and in france.transfusion transmission of the prion, the agent of variant creutzfeldt-jakob disease (vcjd), is now established. subjects infected through food may transmit the disease through blood donations. the two nations most affected to date by this threat are the united kingdom (uk) and france. the first transfusion cases have been observed in the uk over the past 5 years. in france, a few individuals who developed vcjd had a history of blood donation, leading to a risk of transmission to recipients, so ...200919170997
evaluation of 99mtc(co)5i as a potential lung perfusion agent.the use of (99m)tc-macroggregated albumin for lung perfusion imaging is well established in nuclear medicine. however, there have been safety concerns over the use of blood-derived products because of potential contamination by infective agents, for example, variant creutzfeldt jakob disease. preliminary work has indicated that tc(co)(5)i is primarily taken up in the lungs following intravenous administration. the aim of this study was to evaluate the biodistribution and pharmacokinetics of (99m ...200919181271
the impact of social amplification and attenuation of risk and the public reaction to mad cow disease in canada.following the detection of bovine spongiform encephalopathy (bse) in canada, and subsequently in the united states, confidence in the safety of beef products remained high. consumers actually increased their consumption of beef slightly after the news of an increased risk from mad cow disease, which has been interpreted as public support for beef farmers and confidence in government regulators. the canadian public showed a markedly different reaction to the news of domestic bse than the furious ...200919192234
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