scholarly journals Human prion diseases: surgical lessons learned from iatrogenic prion transmission

2016 ◽  
Vol 41 (1) ◽  
pp. E10 ◽  
Author(s):  
David J. Bonda ◽  
Sunil Manjila ◽  
Prachi Mehndiratta ◽  
Fahd Khan ◽  
Benjamin R. Miller ◽  
...  
Keyword(s):  
Prion Disease ◽  
Disease Transmission ◽  
Prion Diseases ◽  
The United States ◽  
Lessons Learned ◽  
World Health ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Prion Transmission ◽  
Iatrogenic Transmission

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 transmission, and a summary of the CDC and WHO guidelines for prevention of prion disease transmission and decontamination of prion-contaminated neurosurgical instruments.

scholarly journals Detection and Control of Prion Diseases in Food Animals

2012 ◽  
Vol 2012 ◽  
pp. 1-24 ◽  
Author(s):  
Peter Hedlin ◽  
Ryan Taschuk ◽  
Andrew Potter ◽  
Philip Griebel ◽  
Scott Napper
Keyword(s):  
Prion Disease ◽  
Disease Transmission ◽  
Management Practices ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Case Scenario ◽  
Worst Case ◽  
Spongiform Encephalopathies ◽  
Food Animals

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.

scholarly journals National Variability in Prion Disease–Related Safety Policies for Neurologic Procedures

2019 ◽  
Vol 9 (4) ◽  
pp. 222-225 ◽  
Author(s):  
Katherine Werbaneth ◽  
Praveen Tummalapalli ◽  
Carl A. Gold
Keyword(s):  
Lumbar Puncture ◽  
Prion Disease ◽  
Prion Diseases ◽  
The United States ◽  
World Health ◽  
Neurosurgical Procedures ◽  
Who Guidelines ◽  
Hospital Policies ◽  
New Guidelines ◽  
Health Organization

Prion diseases are fatal neurodegenerative disorders that can be transmitted via contact with infective tissue. Variability in hospital safety policies related to prion disease may place health-care workers at risk. We sought to assess variability of safety policies related to prion disease for neurosurgical procedures and lumbar punctures among neurological institutions in the United States. We e-mailed neurologists associated with 2016 US News and World Report “Top 50” Neurology & Neurosurgery Institutions to request hospital policies regarding safety precautions related to prion disease. For institutional surgical policies, the main outcome was concordance with each of the 8 specific precautions described in World Health Organization (WHO) guidelines published in 1999. No similar guidelines are available for lumbar puncture, so themes were identified and quantified among the lumbar puncture policies we collected. Of the 51 institutions contacted, there were 38 responses. Two institutions did not have relevant policies and 3 institutions declined to share their policies, yielding 33 institutional policies for review. Of these, 85% had a surgical policy and 54% had a lumbar puncture policy. Concordance with all 8 specific precautions described in the WHO guidelines was found in 14% of surgical policies. Lumbar puncture policies demonstrated variability in methods of waste disposal and decontamination procedures. There is significant variability in policies regarding safety precautions in patients with suspected prion disease. We advocate for the formation of national or international committees to examine this issue, set new guidelines, and foster implementation at the level of individual institutions.

scholarly journals Reduced SOD2 expression does not influence prion disease course or pathology in mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259597
Author(s):  
Simote T. Foliaki ◽  
Brent Race ◽  
Katie Williams ◽  
Chase Baune ◽  
Bradley R. Groveman ◽  
...  
Keyword(s):  
Prion Disease ◽  
Prion Diseases ◽  
Critical Role ◽  
Long Term Potentiation ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Spongiform Encephalopathies ◽  
Knock Out ◽  
Spongiform Change ◽  
Knock Out Mice

Prion diseases are progressive, neurodegenerative diseases affecting humans and animals. Also known as the transmissible spongiform encephalopathies, for the hallmark spongiform change seen in the brain, these diseases manifest increased oxidative damage early in disease and changes in antioxidant enzymes in terminal brain tissue. Superoxide dismutase 2 (SOD2) is an antioxidant enzyme that is critical for life. SOD2 knock-out mice can only be kept alive for several weeks post-birth and only with antioxidant therapy. However, this results in the development of a spongiform encephalopathy. Consequently, we hypothesized that reduced levels of SOD2 may accelerate prion disease progression and play a critical role in the formation of spongiform change. Using SOD2 heterozygous knock-out and litter mate wild-type controls, we examined neuronal long-term potentiation, disease duration, pathology, and degree of spongiform change in mice infected with three strains of mouse adapted scrapie. No influence of the reduced SOD2 expression was observed in any parameter measured for any strain. We conclude that changes relating to SOD2 during prion disease are most likely secondary to the disease processes causing toxicity and do not influence the development of spongiform pathology.

Human prion diseases

2020 ◽  
pp. 6109-6119
Author(s):  
Simon Mead ◽  
R.G. Will
Keyword(s):  
Prion Disease ◽  
Prion Diseases ◽  
Mammalian Species ◽  
Normal Function ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Spongiform Encephalopathies ◽  
Distinct Disease ◽  
Jakob Disease ◽  
Disease Variant

Prion protein (for proteinacious infectious particle) is a membrane-associated glycoprotein present in all mammalian species. Its normal function is unknown, but in prion diseases (also known as transmissible spongiform encephalopathies) a misfolded polymer form of the protein, partially resistant to protease digestion, is deposited in the brain and associated—typically after long incubation periods—with neuronal dysfunction and death. Prion diseases have become the subject of intense scientific and public interest because they are caused by a biologically distinct disease mechanism and because of the implications for public health following the identification of a new human prion disease, variant Creutzfeldt–Jakob disease (vCJD), and the evidence that it is caused by the transmission to humans of a cattle prion disease, bovine spongiform encephalopathy (BSE).

scholarly journals Differential Accumulation of Misfolded Prion Strains in Natural Hosts of Prion Diseases

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2453
Author(s):  
Zoe J. Lambert ◽  
Justin J. Greenlee ◽  
Eric D. Cassmann ◽  
M. Heather West Greenlee
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Prion Diseases ◽  
Brain Regions ◽  
Cellular Prion Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Prion Strains ◽  
Natural Hosts ◽  
Different Strains

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of neurodegenerative protein misfolding diseases that invariably cause death. TSEs occur when the endogenous cellular prion protein (PrPC) misfolds to form the pathological prion protein (PrPSc), which templates further conversion of PrPC to PrPSc, accumulates, and initiates a cascade of pathologic processes in cells and tissues. Different strains of prion disease within a species are thought to arise from the differential misfolding of the prion protein and have different clinical phenotypes. Different strains of prion disease may also result in differential accumulation of PrPSc in brain regions and tissues of natural hosts. Here, we review differential accumulation that occurs in the retinal ganglion cells, cerebellar cortex and white matter, and plexuses of the enteric nervous system in cattle with bovine spongiform encephalopathy, sheep and goats with scrapie, cervids with chronic wasting disease, and humans with prion diseases. By characterizing TSEs in their natural host, we can better understand the pathogenesis of different prion strains. This information is valuable in the pursuit of evaluating and discovering potential biomarkers and therapeutics for prion diseases.

scholarly journals Risk and the Republican National Convention: Application of the Novel COVID-19 Operational Risk Assessment

2021 ◽  
pp. 1-6
Author(s):  
David Callaway ◽  
Jeff Runge ◽  
Lucia Mullen ◽  
Lisa Rentz ◽  
Kevin Staley ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Health Care ◽  
Care Delivery ◽  
The United States ◽  
Lessons Learned ◽  
World Health ◽  
Local Health ◽  
Mass Gathering ◽  
Wide Range ◽  
National Convention

Abstract The United States Centers for Disease Control and Prevention and the World Health Organization broadly categorize mass gathering events as high risk for amplification of coronavirus disease 2019 (COVID-19) spread in a community due to the nature of respiratory diseases and the transmission dynamics. However, various measures and modifications can be put in place to limit or reduce the risk of further spread of COVID-19 for the mass gathering. During this pandemic, the Johns Hopkins University Center for Health Security produced a risk assessment and mitigation tool for decision-makers to assess SARS-CoV-2 transmission risks that may arise as organizations and businesses hold mass gatherings or increase business operations: The JHU Operational Toolkit for Businesses Considering Reopening or Expanding Operations in COVID-19 (Toolkit). This article describes the deployment of a data-informed, risk-reduction strategy that protects local communities, preserves local health-care capacity, and supports democratic processes through the safe execution of the Republican National Convention in Charlotte, North Carolina. The successful use of the Toolkit and the lessons learned from this experience are applicable in a wide range of public health settings, including school reopening, expansion of public services, and even resumption of health-care delivery.

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

2013 ◽  
Vol 94 (12) ◽  
pp. 2819-2827 ◽  
Author(s):  
Rona Wilson ◽  
Karen Dobie ◽  
Nora Hunter ◽  
Cristina Casalone ◽  
Thierry Baron ◽  
...  
Keyword(s):  
Human Health ◽  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Disease Transmission ◽  
Large Scale ◽  
Single Agent ◽  
Diagnostic Methods ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Human Prion Protein

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.

scholarly journals Structural effects of the highly protective V127 polymorphism on human prion protein

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Laszlo L. P. Hosszu ◽  
Rebecca Conners ◽  
Daljit Sangar ◽  
Mark Batchelor ◽  
Elizabeth B. Sawyer ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Structural Changes ◽  
Prion Diseases ◽  
Single Point ◽  
Structural Basis ◽  
Single Point Mutation ◽  
Solution Dynamics ◽  
Human Prion Protein ◽  
Prion Transmission

AbstractPrion diseases, a group of incurable, lethal neurodegenerative disorders of mammals including humans, are caused by prions, assemblies of misfolded host prion protein (PrP). A single point mutation (G127V) in human PrP prevents prion disease, however the structural basis for its protective effect remains unknown. Here we show that the mutation alters and constrains the PrP backbone conformation preceding the PrP β-sheet, stabilising PrP dimer interactions by increasing intermolecular hydrogen bonding. It also markedly changes the solution dynamics of the β2-α2 loop, a region of PrP structure implicated in prion transmission and cross-species susceptibility. Both of these structural changes may affect access to protein conformers susceptible to prion formation and explain its profound effect on prion disease.

Prion disease

2018 ◽  
Author(s):  
Richard Knight
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Prion Diseases ◽  
Human Diseases ◽  
Brain Diseases ◽  
Transmissible Spongiform Encephalopathies ◽  
Structural Form ◽  
Spongiform Encephalopathies ◽  
Spongiform Change ◽  
Neurodegenerative Pathology

Prion diseases (also known as transmissible spongiform encephalopathies (TSEs)) affect animals and humans, although only the human diseases will be discussed in this chapter. Despite TSEs having somewhat disparate causes and effects, there are unifying features: TSEs are brain diseases with neurodegenerative pathology, which is typically associated with spongiform change, and, most characteristically, there is tissue deposition of an abnormal structural form of the prion protein. Some of the TSEs are naturally acquired infections and, while others are not, they are potentially transmissible in certain circumstances.

scholarly journals Prion diseases are efficiently transmitted by blood transfusion in sheep

Blood ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 4739-4745 ◽  
Author(s):  
Fiona Houston ◽  
Sandra McCutcheon ◽  
Wilfred Goldmann ◽  
Angela Chong ◽  
James Foster ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Prion Diseases ◽  
Clinical Signs ◽  
Control Measures ◽  
Spongiform Encephalopathy ◽  
Transmission Rates ◽  
High Transmission ◽  
Jakob Disease ◽  
Natural Scrapie ◽  
Iatrogenic Transmission

Abstract The emergence of variant Creutzfeld-Jakob disease, following on from the bovine spongiform encephalopathy (BSE) epidemic, led to concerns about the potential risk of iatrogenic transmission of disease by blood transfusion and the introduction of costly control measures to protect blood supplies. We previously reported preliminary data demonstrating the transmission of BSE and natural scrapie by blood transfusion in sheep. The final results of this experiment, reported here, give unexpectedly high transmission rates by transfusion of 36% for BSE and 43% for scrapie. A proportion of BSE-infected tranfusion recipients (3 of 8) survived for up to 7 years without showing clinical signs of disease. The majority of transmissions resulted from blood collected from donors at more than 50% of the estimated incubation period. The high transmission rates and relatively short and consistent incubation periods in clinically positive recipients suggest that infectivity titers in blood were substantial and/or that blood transfusion is an efficient method of transmission. This experiment has established the value of using sheep as a model for studying transmission of variant Creutzfeld-Jakob disease by blood products in humans.

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