scholarly journals Wide distribution of prion infectivity in the peripheral tissues of vCJD and sCJD patients

2021 ◽  
Vol 141 (3) ◽  
pp. 383-397
Author(s):  
Jean-Yves Douet ◽  
Alvina Huor ◽  
Hervé Cassard ◽  
Séverine Lugan ◽  
Naima Aron ◽  
...  
Keyword(s):  
Prion Disease ◽  
Wide Distribution ◽  
Human Prion Disease ◽  
Marked Contrast ◽  
Peripheral Tissues ◽  
Spontaneous Formation ◽  
Prion Infectivity ◽  
Clinical Procedures ◽  
Jakob Disease ◽  
The Central Nervous System

AbstractSporadic Creutzfeldt-Jakob disease (sCJD) is the commonest human prion disease, occurring most likely as the consequence of spontaneous formation of abnormal prion protein in the central nervous system (CNS). Variant Creutzfeldt–Jakob disease (vCJD) is an acquired prion disease that was first identified in 1996. In marked contrast to vCJD, previous investigations in sCJD revealed either inconsistent levels or an absence of PrPSc in peripheral tissues. These findings contributed to the consensus that risks of transmitting sCJD as a consequence of non-CNS invasive clinical procedures were low. In this study, we systematically measured prion infectivity levels in CNS and peripheral tissues collected from vCJD and sCJD patients. Unexpectedly, prion infectivity was detected in a wide variety of peripheral tissues in sCJD cases. Although the sCJD infectivity levels varied unpredictably in the tissues sampled and between patients, these findings could impact on our perception of the possible transmission risks associated with sCJD.

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.

scholarly journals Central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease

2008 ◽  
Vol 363 (1510) ◽  
pp. 3755-3763 ◽  
Author(s):  
Sebastian Brandner ◽  
Jerome Whitfield ◽  
Ken Boone ◽  
Anderson Puwa ◽  
Catherine O'Malley ◽  
...  
Keyword(s):  
Prion Protein ◽  
Human Prion Disease ◽  
Peripheral Tissues ◽  
Prion Strain ◽  
Pathological Analysis ◽  
Lymphoreticular Tissue ◽  
Jakob Disease ◽  
Strain Type ◽  
Few Data ◽  
The Brain

While the neuropathology of kuru is well defined, there are few data concerning the distribution of disease-related prion protein in peripheral tissues. Here we report the investigation of brain and peripheral tissues from a kuru patient who died in 2003. Neuropathological findings were compared with those seen in classical (sporadic and iatrogenic) Creutzfeldt–Jakob disease (CJD) and variant CJD (vCJD). The neuropathological findings of the kuru patient showed all the stereotypical changes that define kuru, with the occurrence of prominent PrP plaques throughout the brain. Lymphoreticular tissue showed no evidence of prion colonization, suggesting that the peripheral pathogenesis of kuru is similar to that seen in classical CJD rather than vCJD. These findings now strongly suggest that the characteristic peripheral pathogenesis of vCJD is determined by prion strain type alone rather than route of infection.

scholarly journals Kuru, the First Human Prion Disease

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 232 ◽  
Author(s):  
Paweł Liberski ◽  
Agata Gajos ◽  
Beata Sikorska ◽  
Shirley Lindenbaum
Keyword(s):  
Electron Microscopy ◽  
Confocal Microscopy ◽  
Prion Disease ◽  
Amyloid Plaques ◽  
Human Medicine ◽  
Spongiform Encephalopathy ◽  
Biomedical Sciences ◽  
Human Prion Disease ◽  
History Of ◽  
Jakob Disease

Kuru, the first human prion disease was transmitted to chimpanzees by D. Carleton Gajdusek (1923–2008). In this review, we summarize the history of this seminal discovery, its anthropological background, epidemiology, clinical picture, neuropathology, and molecular genetics. We provide descriptions of electron microscopy and confocal microscopy of kuru amyloid plaques retrieved from a paraffin-embedded block of an old kuru case, named Kupenota. The discovery of kuru opened new vistas of human medicine and was pivotal in the subsequent transmission of Creutzfeldt–Jakob disease, as well as the relevance that bovine spongiform encephalopathy had for transmission to humans. The transmission of kuru was one of the greatest contributions to biomedical sciences of the 20th century.

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 Skin RT-QuIC Assays are More Sensitive than CSF RT-QuIC in Prion Detection for Chinese Probable Sporadic Creutzfeldt-Jakob Disease

2020 ◽  
Author(s):  
Kang Xiao ◽  
Xue-Hua Yang ◽  
Wei Zhou ◽  
Cao Chen ◽  
Brian S Appleby ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Prion Disease ◽  
Preliminary Data ◽  
High Sensitivity ◽  
Definite Diagnosis ◽  
Human Prion Disease ◽  
Diagnostic Potential ◽  
Jakob Disease ◽  
The Brain ◽  
Skin Specimen

Abstract BackgroundThe definite diagnosis of human sporadic Creutzfeldt-Jakob disease (sCJD) largely depends on postmortem neuropathology and PrPSc detection in the brain. The development of prion RT-QuIC of cerebrospinal fluid (CSF) samples makes it possible for premortem diagnosis for sCJD. However the diagnostic potential of RT-QuIC of skin specimen for probable sCJD is not well researched. This study is to evaluate the diagnostic potential of RT-QuIC of skin specimen in human prion diseases.MethodsWe collected the paired skin and CSF samples from 29 recruited alive patients referred to Chinese CJD surveillance center, including 12 probable sCJD, 9 non-CJD, 3 genetic prion disease (gPrD) and 5 cases whose diagnoses still pending. The samples were subjected to RT-QuIC assays using recombinant hamster PrP protein rHaPrP90-231 as the substrate.ResultsAll 12 probable sCJD patients, 4 pending, and 1 T188K genetic CJD (gCJD) cases showed positive prion-seeding activity, while all 9 non-CJD patients were negative. CSF RT-QuIC positive seeding activity was only observed in 5 probable sCJD patients.ConclusionsOur preliminary data indicate high sensitivity and specificity of skin RT-QuIC in prion detection for Chinese probable sCJD and highlight that skin prion-seeding activity is a reliable biomarker for premortem diagnosis of human prion disease.

scholarly journals Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2018

2019 ◽  
Vol 43 ◽  
Author(s):  
Christine Stehmann ◽  
Matteo Senesi ◽  
Victoria Lewis ◽  
Mairin Ummi ◽  
Marion Simpson ◽  
...  
Keyword(s):  
Prion Disease ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathies ◽  
Annual Number ◽  
Human Prion Disease ◽  
Prospective Surveillance ◽  
Surveillance Period ◽  
Spongiform Encephalopathies ◽  
Jakob Disease ◽  
Neuropathological Examination

Nationwide surveillance of human prion diseases (also known as transmissible spongiform encephalopathies), the most common being Creutzfeldt-Jakob disease (CJD), is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR), based at the University of Melbourne. 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 relation to pre-mortem diagnostics, the delineation of new disease subtypes and a heightened awareness of prion diseases in health care settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR from 1 January to 31 December 2018. 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 2018, 465 domestic CSF specimens were referred for 14-3-3 protein testing and 78 persons with suspected human prion disease were formally added to the national register. The majority of the 78 suspect case notifications remain as of 31 December 2018 classified as “incomplete” (42 cases), while eleven cases were excluded by either detailed clinical follow-up (one case) or neuropathological examination (ten cases); 15 cases were classified as “definite” and ten as “probable” prion disease. Sixty-two percent of all suspected human prion disease related deaths underwent neuropathological examination. No cases of variant CJD were confirmed.

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 Rapidly Progressing Sporadic Creutzfeldt-Jakob Disease Presenting as a Stroke

2018 ◽  
Vol 10 (3) ◽  
pp. 261-265 ◽  
Author(s):  
Maxim Oliver ◽  
Lisa Dyke ◽  
Alex Rico ◽  
Mario Madruga ◽  
Jorge Parellada ◽  
...  
Keyword(s):  
Prion Disease ◽  
Neurological Disorders ◽  
Hospice Care ◽  
Clinical Suspicion ◽  
Spongiform Encephalopathy ◽  
Medical Procedures ◽  
Human Prion Disease ◽  
Progressive Dementia ◽  
History Of ◽  
Jakob Disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare, fatal human prion disease that is characterized by progressive dementia and neurologic degeneration. It can mimic multiple other neurological disorders, and a high index of clinical suspicion is necessary to make a diagnosis. A 74-year-old woman with a 3-month history of a stroke and progressive neurologic deterioration was found to have sCJD. She expired within a week of her diagnosis. Autopsy revealed spongiform encephalopathy consistent with prion disease, and genetic analysis revealed 129 polymorphism and no pathologic mutation, confirming the diagnosis of nonfamilial human prion disease. No pathologic evidence of a stroke was found. Awareness of the disease by clinicians is important not only at the time of initial presentation but also during the following months. Since there is no treatment, invasive medical procedures should be limited to only those that are required for either diagnosis or hospice care.

scholarly journals Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2020 Erratum to Commun Dis Intell (2018) 2021;45 (https://doi.org/10.33321/cdi.2021.45.38)

2021 ◽  
Vol 45 ◽  
Author(s):  
Christiane Stehmann ◽  
Matteo Senesi ◽  
Shannon Sarros ◽  
Amelia McGlade ◽  
Victoria Lewis ◽  
...  
Keyword(s):  
Prion Disease ◽  
Disease Surveillance ◽  
Prion Diseases ◽  
Annual Number ◽  
Human Prion Disease ◽  
Prospective Surveillance ◽  
Surveillance Period ◽  
Healthcare Settings ◽  
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 2020. 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 2020, 510 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 2020, just over half (44 cases) of the 85 suspect case notifications remain classified as ‘incomplete’; 12 cases were excluded through either detailed clinical follow-up (8 cases) or neuropathological examination (4 cases); 18 cases were classified as ‘definite’ and eleven as ‘probable’ prion disease. For 2020, sixty percent of all suspected human-prion-disease-related deaths in Australia underwent neuropathological examination. No cases of variant or iatrogenic CJD were identified. The SARS-CoV-2 pandemic did not affect prion disease surveillance outcomes in Australia.

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