scholarly journals Variant CJD: Reflections a Quarter of a Century on

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1413
Author(s):  
Diane L Ritchie ◽  
Alexander H Peden ◽  
Marcelo A Barria
Keyword(s):  
Prion Disease ◽  
Prion Diseases ◽  
Large Body ◽  
Dietary Exposure ◽  
Spongiform Encephalopathy ◽  
Biochemical Phenotype ◽  
Jakob Disease ◽  
Asymptomatic Individuals ◽  
The Uk ◽  
The Impact

Twenty-five years has now passed since variant Creutzfeldt-Jakob disease (vCJD) was first described in the United Kingdom (UK). Early epidemiological, neuropathological and biochemical investigations suggested that vCJD represented a new zoonotic form of human prion disease resulting from dietary exposure to the bovine spongiform encephalopathy (BSE) agent. This hypothesis has since been confirmed though a large body of experimental evidence, predominantly using animal models of the disease. Today, the clinical, pathological and biochemical phenotype of vCJD is well characterized and demonstrates a unique and remarkably consistent pattern between individual cases when compared to other human prion diseases. While the numbers of vCJD cases remain reassuringly low, with 178 primary vCJD cases reported in the UK and a further 54 reported worldwide, concerns remain over the possible appearance of new vCJD cases in other genetic cohorts and the numbers of asymptomatic individuals in the population harboring vCJD infectivity. This review will provide a historical perspective on vCJD, examining the origins of this acquired prion disease and its association with BSE. We will investigate the epidemiology of the disease along with the unique clinicopathological and biochemical phenotype associated with vCJD cases. Additionally, this review will examine the impact vCJD has had on public health in the UK and the ongoing concerns raised by this rare group of disorders.

Prion disease

2012 ◽  
pp. 351-361
Author(s):  
John Collinge
Keyword(s):  
Diagnostic Criteria ◽  
Prion Disease ◽  
Prion Diseases ◽  
Case Reports ◽  
Neuronal Loss ◽  
Dietary Exposure ◽  
Spongiform Encephalopathy ◽  
Spongiform Encephalopathies ◽  
Jakob Disease ◽  
Classical Triad

The human prion diseases, also known as the subacute spongiform encephalopathies, have been traditionally classified into Creutzfeldt–Jakob disease (CJD), Gerstmann–Sträussler syndrome (GSS) (also known as Gerstmann–Sträussler–Scheinker disease), and kuru. Although rare, affecting about 1–2 per million worldwide per annum, remarkable attention has been recently focused on these diseases. This is because of the unique biology of the transmissible agent or prion, and also because bovine spongiform encephalopathy (BSE), an epidemic bovine prion disease, appears to have transmitted to humans as variant CJD (vCJD), opening the possibility of a significant threat to public health through dietary exposure to infected tissues. The transmissibility of the human diseases was demonstrated with the transmission, by intracerebral inoculation with brain homogenates into chimpanzees, of first kuru and then CJD in 1966 and 1968, respectively. Transmission of GSS followed in 1981. The prototypic prion disease is scrapie, a naturally occurring disease of sheep and goats, which has been recognized in Europe for over 200 years and which is present in the sheep flocks of many countries. Scrapie was demonstrated to be transmissible by inoculation in 1936 and the recognition that kuru, and then CJD, resembled scrapie in its histopathological appearances led to the suggestion that these diseases may also be transmissible. Kuru reached epidemic proportions amongst the Fore linguistic group in the Eastern Highlands of Papua New Guinea and was transmitted by ritual cannibalism. Since the cessation of cannibalism in the 1950s the disease has declined but a few cases still occur as a result of the long incubation periods in this condition, which may exceed 50 years. The term Creutzfeldt–Jakob disease was introduced by Spielmeyer in 1922 bringing together the case reports published by Creutzfeldt and Jakob. Several of these cases would not meet modern diagnostic criteria for CJD and indeed it was not until the demonstration of transmissibility allowed diagnostic criteria to be reassessed and refined that a clear diagnostic entity developed. All these diseases share common histopathological features; the classical triad of spongiform vacuolation (affecting any part of the cerebral grey matter), astrocytic proliferation, and neuronal loss, may be accompanied by the deposition of amyloid plaques.

scholarly journals Projections of the future course of the primary vCJD epidemic in the UK: inclusion of subclinical infection and the possibility of wider genetic susceptibility

2005 ◽  
Vol 2 (2) ◽  
pp. 19-31 ◽  
Author(s):  
Paul Clarke ◽  
Azra C Ghani
Keyword(s):  
Blood Transfusion ◽  
Small Proportion ◽  
Spongiform Encephalopathy ◽  
Subclinical Infection ◽  
The United Kingdom ◽  
Jakob Disease ◽  
The Uk ◽  
The Impact ◽  
Primary Transmission ◽  
Clinical Cases

The incidence of variant Creutzfeldt–Jakob disease (vCJD) in the United Kingdom appears to be in decline, with only four deaths reported this year (to 6 September 2004). However, results of a survey of lymphoreticular tissues have suggested a substantially higher prevalence of vCJD than expected from the clinical data alone. There are two plausible explanations for this discrepancy: first, a proportion of those infected will not develop clinical disease (subclinical infection); and second, the genetic group in which no clinical cases of vCJD have yet occurred is susceptible. Using mathematical models for the primary transmission of bovine spongiform encephalopathy to humans, we explore the impact of these hypotheses on case predictions. Under the first hypothesis, the results suggest relatively few future cases will arise via primary transmission, but that these cases are a small proportion of those infected, with most having subclinical infection. Under the second hypothesis, results suggest a maximum fivefold increase in cases, but this hypothesis is unable to account for the discrepancy between clinical cases and the estimated prevalence. Predictions of future cases of vCJD therefore remain uncertain, particularly given the recent identification of additional cases infected via blood transfusion.

scholarly journals Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2019

2020 ◽  
Vol 44 ◽  
Author(s):  
Christiane Stehmann ◽  
Matteo Senesi ◽  
Shannon Sarros ◽  
Amelia McGlade ◽  
Marion Simpson ◽  
...  
Keyword(s):  
Prion Disease ◽  
Disease Surveillance ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Annual Number ◽  
Spongiform Encephalopathy ◽  
Human Prion Disease ◽  
Prospective Surveillance ◽  
Jakob Disease ◽  
Neuropathological Examination

Nationwide surveillance of Creutzfeldt-Jakob disease and other human prion diseases is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR). National surveillance encompasses the period since 1 January 1970, with prospective surveillance occurring from 1 October 1993. Over this prospective surveillance period, considerable developments have occurred in pre-mortem diagnostics; in the delineation of new disease subtypes; and in a heightened awareness of prion diseases in healthcare settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR during 2019. Since the ANCJDR began offering diagnostic cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased. In 2019, 513 domestic CSF specimens were referred for 14-3-3 protein testing and 85 persons with suspected human prion disease were formally added to the national register. As of 31 December 2019, just under half (42 cases) of the 85 suspect case notifications remain classified as ‘incomplete’; 16 cases were excluded through either detailed clinical follow-up (3 cases) or neuropathological examination (13 cases); 20 cases were classified as ‘definite’ and seven as ‘probable’ prion disease. For 2019, sixty-three percent of all suspected human prion disease related deaths in Australia underwent neuropathological examination. No cases of variant or iatrogenic CJD were identified. Two possibly causal novel prion protein gene (PRNP) sequence variations were identified. Keywords: Creutzfeldt-Jakob disease, prion disease, transmissible spongiform encephalopathy, disease surveillance

scholarly journals Study protocol for enhanced CJD surveillance in the 65+ years population group in Scotland: an observational neuropathological screening study of banked brain tissue donations for evidence of prion disease

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e033744
Author(s):  
Alexander Howard Peden ◽  
Lovney Kanguru ◽  
Diane L Ritchie ◽  
Colin Smith ◽  
Anna M Molesworth
Keyword(s):  
Brain Tissue ◽  
Prion Disease ◽  
Age Of Onset ◽  
Population Group ◽  
Immunohistochemical Analysis ◽  
Spongiform Encephalopathy ◽  
Human Prion Disease ◽  
Tissue Samples ◽  
Jakob Disease ◽  
The Uk

IntroductionCreutzfeldt-Jakob disease (CJD) is a human prion disease that occurs in sporadic, genetic and acquired forms. Variant CJD (vCJD) is an acquired form first identified in 1996 in the UK. To date, 178 cases of vCJD have been reported in the UK, most of which have been associated with dietary exposure to the bovine spongiform encephalopathy agent. Most vCJD cases have a young age of onset, with a median age at death of 28 years. In the UK, suspected cases of vCJD are reported to the UK National Creutzfeldt-Jakob Disease Research & Surveillance Unit (NCJDRSU). There is, however, a concern that the national surveillance system might be missing some cases of vCJD or other forms of human prion disease, particularly in the older population, perhaps because of atypical clinical presentation. This study aims to establish whether there is unrecognised prion disease in people aged 65 years and above in the Scottish population by screening banked brain tissue donated to the Edinburgh Brain Bank (EBB).MethodsNeuropathological screening of prospective and retrospective brain tissue samples is performed. This involves histopathological and immunohistochemical analysis and prion protein biochemical analysis. During the study, descriptive statistics are used to describe the study population, including the demographics and clinical, pathological and referral characteristics. Controlling for confounders, univariate and multivariate analyses will be used to compare select characteristics of newly identified suspect cases with previously confirmed cases referred to the NCJDRSU.Ethics and disseminationBrain tissue donations to EBB are made voluntarily by the relatives of patients, with consent for use in research. The EBB has ethical approval to provide tissue samples to research projects (REC reference 16/ES/0084). The findings of this study will be disseminated in meetings, conferences, workshops and as peer-reviewed publications.Trial registration numbers10/S1402/69 and 10/S1402/70

scholarly journals A field on fire: The biochemistry of mad cows

2005 ◽  
Vol 27 (4) ◽  
pp. 6-8
Author(s):  
David R. Brown
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Prion Disease ◽  
Prion Diseases ◽  
Human Diseases ◽  
Spongiform Encephalopathy ◽  
Related Disease ◽  
Jakob Disease ◽  
Sporadic Cjd

Prion diseases are neurodegenerative diseases1 that have been linked together because they may potentially have the same cause. These include the diseases scrapie of sheep and BSE (bovine spongiform encephalopathy) of cattle, and also several human diseases that include sporadic CJD (Creutzfeldt-Jakob) disease and a variety of inherited forms. The inherited forms of prion diseases are linked to mutations within the gene for the prion protein. Around 85% of all human cases of prion disease are sporadic CJD, which is a disease affecting people of around 60 years of age. The cause of this disease remains unknown. Unfortunately, the name of this disease causes some confusion, as it is similar to vCJD (variant CJD), a related disease of much younger people.

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).

Genetic Factors in Mammalian Prion Diseases

2019 ◽  
Vol 53 (1) ◽  
pp. 117-147 ◽  
Author(s):  
Simon Mead ◽  
Sarah Lloyd ◽  
John Collinge
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Protein Interactions ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Spongiform Encephalopathy ◽  
Cellular Functions ◽  
Modifying Factors ◽  
Jakob Disease ◽  
The Central Nervous System

Mammalian prion diseases are a group of neurodegenerative conditions caused by infection of the central nervous system with proteinaceous agents called prions, including sporadic, variant, and iatrogenic Creutzfeldt-Jakob disease; kuru; inherited prion disease; sheep scrapie; bovine spongiform encephalopathy; and chronic wasting disease. Prions are composed of misfolded and multimeric forms of the normal cellular prion protein (PrP). Prion diseases require host expression of the prion protein gene ( PRNP) and a range of other cellular functions to support their propagation and toxicity. Inherited forms of prion disease are caused by mutation of PRNP, whereas acquired and sporadically occurring mammalian prion diseases are controlled by powerful genetic risk and modifying factors. Whereas some PrP amino acid variants cause the disease, others confer protection, dramatically altered incubation times, or changes in the clinical phenotype. Multiple mechanisms, including interference with homotypic protein interactions and the selection of the permissible prion strains in a host, play a role. Several non- PRNP factors have now been uncovered that provide insights into pathways of disease susceptibility or neurotoxicity.

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 The most problematic symptoms of prion disease – an analysis of carer experiences

2018 ◽  
Vol 31 (08) ◽  
pp. 1181-1190
Author(s):  
Liz Ford ◽  
Peter Rudge ◽  
Kathy Robinson ◽  
John Collinge ◽  
Michele Gorham ◽  
...  
Keyword(s):  
Outcome Measures ◽  
Prion Disease ◽  
Prion Diseases ◽  
Formal Analysis ◽  
Structured Interview ◽  
Disease Stage ◽  
Structured Interviews ◽  
Wide Range ◽  
The Uk ◽  
And Behavior

ABSTRACTObjectives:Prion diseases are rare dementias that most commonly occur sporadically, but can be inherited or acquired, and for which there is no cure. We sought to understand which prion disease symptoms are most problematic for carers, to inform the development of outcome measures.Design:Self-completed questionnaire with follow-up of a subset of participants by structured interview.Setting:A nested study in the UK National Prion Monitoring Cohort, a longitudinal observational study.Participants and measurements:71 carers, of people with different prion diseases with a wide range of disease severity, identified 236 of their four most problematic symptoms by questionnaire which were grouped into ten domains. Structured interviews were then done to qualitatively explore these experiences. Eleven family carers of people with prion disease were selected, including those representative of a range of demographics and disease subtypes and those who cared for people with prion disease, living or recently deceased. Interviews were transcribed and formally studied.Results:The six most problematic symptom domains were: mobility and coordination; mood and behavior; personal care and continence; eating and swallowing; communication; and cognition and memory. The prevalence of these symptoms varied significantly by disease stage and type. A formal analysis of structured interviews to explore these domains is reported.Conclusions:We make suggestions about how healthcare professionals can focus their support for people with prion disease. Clinical trials that aim to generate evidence regarding therapies that might confer meaningful benefits to carers should consider including outcome measures that monitor the symptomatic domains we have identified as problematic.

The neuroepidemiology of human prion disease

2020 ◽  
pp. 367-378
Author(s):  
Patrick JM Urwin ◽  
Anna M Molesworth
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Prion Protein Gene ◽  
Human Prion Disease ◽  
Disease States ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Sporadic Disease

Human prion diseases comprise a number of rare and fatal neurodegenerative conditions that result from the accumulation in the central nervous system of an abnormal form of a naturally occurring protein, called the prion protein. The diseases occur in genetic, sporadic, and acquired forms: genetic disease is associated with mutations in the prion protein gene (PRNP); sporadic disease is thought to result from a spontaneous protein misfolding event; acquired disease results from transmission of infection from an animal or another human. The potential transmissibility of the prion in any of these forms, either in disease states or during the incubation period, has implications for public health. Here we focus on Creutzfeldt-Jakob Disease (CJD), including variant Creutzfeldt-Jakob Disease (vCJD), although we will also discuss other forms of human prion disease.

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