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Abstract Treatment with human pituitary-derived growth hormone (hGH) was responsible for a significant proportion of iatrogenic Creutzfeldt–Jakob disease (iCJD) cases. France and the UK experienced the largest case numbers of hGH-iCJD, with 122 and 81 cases respectively. Differences in the frequency of the three PRNP codon 129 polymorphisms (MM, MV and VV) and the estimated incubation periods associated with each of these genotypes in the French and the UK hGH-iCJD cohorts led to the suggestion that the prion strains responsible for these two hGH-iCJD cohorts were different. In this study, we characterized the prion strains responsible for hGH-iCJD cases originating from UK (n = 11) and France (n = 11) using human PrP expressing mouse models. The cases included PRNP MM, MV and VV genotypes from both countries. UK and French sporadic CJD (sCJD) cases were included as controls. The prion strains identified following inoculation with hGH-iCJD homogenates corresponded to the two most frequently observed sCJD prion strains (M1CJD and V2CJD). However, in clear contradiction to the initial hypothesis, the prion strains that were identified in the UK and the French hGH-iCJD cases were not radically different. In the vast majority of the cases originating from both countries, the V2CJD strain or a mixture of M1CJD + V2CJD strains were identified. These data strongly support the contention that the differences in the epidemiological and genetic profiles observed in the UK and France hGH-iCJD cohorts cannot be attributed only to the transmission of different prion strains.

Treatment with human pituitary-derived growth hormone (hGH) was responsible for a significant proportion of iatrogenic Creutzfeldt–Jakob disease (iCJD) cases. France and the UK experienced the largest case numbers of hGH-iCJD, with 122 and 81 cases respectively. Differences in the frequency of the three PRNP codon 129 polymorphisms (MM, MV and VV) and the estimated incubation periods associated with each of these genotypes in the French and the UK hGH-iCJD cohorts led to the suggestion that the prion strains responsible for these two hGH-iCJD cohorts were different. In this study, we characterized the prion strains responsible for hGH-iCJD cases originating from UK (n = 11) and France (n = 11) using human PrP expressing mouse models. The cases included PRNP MM, MV and VV genotypes from both countries. UK and French sporadic CJD (sCJD) cases were included as controls. The prion strains identified following inoculation with hGH-iCJD homogenates corresponded to the two most frequently observed sCJD prion strains (M1CJD and V2CJD). However, in clear contradiction to the initial hypothesis, the prion strains that were identified in the UK and the French hGH-iCJD cases were not radically different. In the vast majority of the cases originating from both countries, the V2CJD strain or a mixture of M1CJD + V2CJD strains were identified. These data strongly support the contention that the differences in the epidemiological and genetic profiles observed in the UK and France hGH-iCJD cohorts cannot be attributed only to the transmission of different prion strains. [ABSTRACT FROM AUTHOR]

This paper is intended to discuss some of the scientific and ethical issues that are created by increased research efforts towards earlier diagnosis, as well as to treatment of, human prion diseases (and related dementias), including the resulting consequences for individuals, their families, and society. Most patients with prion disease currently are diagnosed when they are about 2/3 of the way through their disease course (Geschwind et al., 2010a; Paterson et al., 2012b), when the disease has progressed so far that even treatments that stop the disease process would probably have little benefit. Although there are currently no treatments available for prion diseases, we and others have realized that we must diagnose patients earlier and with greater accuracy so that future treatments have hope of success. As approximately 15% of prion diseases have a autosomal dominant genetic etiology, this further adds to the complexity of ethical issues, particularly regarding when to conduct genetic testing, release of genetic results, and when or if to implement experimental therapies. Human prion diseases are both infectious and transmissible; great care is required to balance the needs of the family and individual with both public health needs and strained hospital budgets. It is essential to proactively examine and address the ethical issues involved, as well as to define and in turn provide best standards of care.

The unanticipated diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) in a patient after previous neurosurgery can lead to difficult decisions regarding informing contacts. A patient developed sCJD 3 years after neurosurgery. There were 29 potential contacts and 26 were contacted. Twelve completed a questionnaire. The majority of patients wished to know about the contact and to be seen face-to-face, and their main concern was developing the disease despite verbal and written reassurance that this was unlikely. Informing patients of sCJD contact is difficult and can lead to significant patient anxiety. Face-to-face meetings, a helpline and follow-up can help. [ABSTRACT FROM AUTHOR]

Doped diamond-like carbon (DLC) coatings offer potential antifouling surfaces against microbial and protein attachment. In particular, stainless steel surgical instruments are subject to tissue protein and resilient prion protein attachment, making decontamination methods used in sterile service departments ineffective, potentially increasing the risk of iatrogenic Creutzfeldt-Jakob disease during surgical procedures. This study examined the adsorption of proteins and prion-associated amyloid to doped DLC surfaces and the efficacy of commercial cleaning chemistries applied to these spiked surfaces, compared to titanium nitride coating and stainless steel. Surfaces inoculated with ME7-infected brain homogenate were visualised using SYPRO Ruby/Thioflavin T staining and modified epi-fluorescence microscopy before and after cleaning. Reduced protein and prion amyloid contamination was observed on the modified surfaces and subsequent decontamination efficacy improved. This highlights the potential for a new generation of coatings for surgical instruments to reduce the risk of iatrogenic CJD infection. [ABSTRACT FROM AUTHOR]

Creutzfeld-Jakob disease (CJD) belongs to the group of human prion diseases - rare neurodegenerative disorders that are caused by transmissible agents known as prions. In CJD, the levels of prion infectivity are highest in the brain, and there is evidence from experimental models that similar levels of infectivity are likely to be present in the retina and optic nerve. CJD has been transmitted by corneal transplantation and there have been increasing concerns that transmission by ophthalmic surgery (particularly retinal surgery) is a possibility. This article outlines the current information on ocular tissue involvement in CJD, discusses concerns regarding the risk of potential transmission and addresses current issues for risk management in ophthalmic surgery. [ABSTRACT FROM AUTHOR]

Background: One definite, one probable and several possible transmissions of sporadic Creutzfeldt–Jakob disease (sCJD) have followed corneal transplantation. We report an incident in the UK in 1997 in which both corneas and scleras from a donor, subsequently confirmed to have had sCJD, were transplanted. The final clinical outcome for two surviving recipients is still not yet known. Case report: In 1997, a 56-year-old woman died from biopsy-proven carcinoma of the bronchus. Both eyes were donated for transplantation. Shortly before she died, she had developed neurological symptoms thought to be due to brain metastases. However, the final result of a neurological post-mortem examination revealed evidence of sCJD. By this time the corneas had been transplanted, one 3 months previously into a 40-year-old man for keratoconus and the other 4 months previously into an 85-year-old woman for Fuchs’ dystrophy. In addition, both scleras had been transplanted into a 36-year-old man undergoing oculoplastic reconstructive surgery. The surgeons and patients were informed and removal of tissue was advised but undertaken in only two of the patients. Immunohistochemistry failed to demonstrate the presence of the abnormal form of the prion protein in explanted tissue. Conclusions: Eight years after the event, two patients remain free of symptoms suggestive of iatrogenic CJD ( ). The third having died aged 92 years, some 7 years after surgery, showing signs of dementia not considered indicative of iatrogenic CJD. Nevertheless this adverse incident attracted substantial publicity. Coupled with continuing concerns in the UK about person-to-person transmission of variant CJD, this has lead to a number of important consequences in donor eye retrieval, ocular tissue banking and transplantation. [ABSTRACT FROM AUTHOR]

Summary: Reduction of the initial bioburden on instruments, prior to sterilization, is believed to reduce transmission risks of iatrogenic Creutzfeldt-Jakob disease. Endodontic files are used in the preparation of root canals and are likely to have close contact and become contaminated with neural material from branches of the maxillary and mandibular cranial nerves. This study examined methods used by 22 dental practices to clean endodontic files, and scored visible debris and residual protein levels adhering to 220 dental endodontic files that had been used, cleaned, autoclaved and were deemed ready for re-use. Visible debris was scored after examination under a dissecting light microscope. Residual protein was quantified using a fluorescent assay based on reaction of proteins with o-phthaldialdehyde/N-acetyl cysteine. There was wide variation in the methods used by practices to clean endodontic files. The cleaning process varied from a wipe with an alcohol-impregnated cloth to hand scrubbing and/or use of an ultrasonic bath. Surface debris was visually detected on 98% of files. Residual protein was detected on all the files examined (median amount: 5.4μg; range: 0.5–63.2μg). These results demonstrate that the cleaning of some instruments reprocessed routinely in primary care is incomplete, and such instruments cannot be excluded as a potential source of cross-infection. [Copyright &y& Elsevier]

Human prion diseases including sporadic Creutzfeldt-Jakob disease (sCJD), inherited prion diseases, and acquired human prion diseases are lethal neurodegenerative diseases. One of the major sources of iatrogenic Creutzfeldt-Jakob disease was human growth hormone (hGH-iCJD) derived from contaminated cadaveric pituitaries. The incidence of hGH-iCJD has decreased since changing from growth hormone extracted from human cadaveric pituitaries to recombinant pituitary hormones. However, extensive analysis on the localization and detecting of abnormal prion protein in the pituitary gland are limited. In this study, we examined 9 autopsied brains and pituitary glands from 6 patients with prion disease (3 Gerstmann-Sträussler-Scheinker disease, 2 sCJD, and 1 dura mater graft-associated CJD) and 3 individuals with nonprion diseases. Western blot analysis of pituitary samples demonstrated unique glycoforms of normal cellular prion protein with molecular weights of 30-40 kDa, which was higher than the typical 25-35 kDa prion protein in brains. Proteomic analysis also revealed prion protein approximately the molecular weight of 40 kDa in pituitary samples. Moreover, proteinase K-resistant Prion protein was frequently detected in pituitary samples of the prion diseases. Immunohistochemistry for Prion protein revealed mosaic cellular distribution preferentially in growth hormone- or prolactin-producing cells., (© 2019 American Association of Neuropathologists, Inc. All rights reserved.)

Prion diseases are progressive fatal encephalopathies characterized by a neurodegenerative pathology, the tissue deposition of abnormally folded prion protein and, in general, potential transmissibility. Creutzfeldt-Jakob disease (CJD) is the commonest human prion disease and occurs in three principal forms: sporadic (idiopathic), acquired (infectious), and inherited (genetic). This chapter concerns the sporadic and acquired forms. Sporadic CJD occurs worldwide and affects mainly the middle aged and elderly. There are recognized genetic risk factors-most importantly the PRNP-129 polymorphism. The acquired forms of CJD consist of iatrogenic CJD (accidental transmission of CJD via medical or surgical procedures) and variant CJD (vJCD) (which originated as a zoonosis via bovine spongiform encephalopathy (BSE)-contamination of human food). The main causes of iatrogenic CJD are cadaveric-derived human growth hormone treatment and dura mater surgical grafts. The PRNP-129 polymorphism has important effects on iatrogenic infection, including overall susceptibility and incubation period. vCJD, resulting from dietary exposure to BSE, has affected mostly the United Kingdom, followed by France. All tested cases were originally PRNP-129MM, although two MV cases have been identified recently (one possible; one definite). vCJD has been secondarily transmitted via blood transfusion and a blood product. There is continuing concern over secondary transmission since there is evidence-from lymphoreticular tissue studies-of extensive subclinical infection in the UK general population, although a further recent study has caused uncertainty over the significance of the previous studies. While definitive diagnosis of CJD is pathological, recent developments in protein amplification and detection have led to significantly better clinical diagnosis., (© 2017 Elsevier Inc. All rights reserved.)

This paper is intended to discuss some of the scientific and ethical issues that are created by increased research efforts towards earlier diagnosis, as well as to treatment of, human prion diseases (and related dementias), including the resulting consequences for individuals, their families, and society. Most patients with prion disease currently are diagnosed when they are about 2/3 of the way through their disease course (Geschwind et al., 2010a; Paterson et al., 2012b), when the disease has progressed so far that even treatments that stop the disease process would probably have little benefit. Although there are currently no treatments available for prion diseases, we and others have realized that we must diagnose patients earlier and with greater accuracy so that future treatments have hope of success. As approximately 15% of prion diseases have a autosomal dominant genetic etiology, this further adds to the complexity of ethical issues, particularly regarding when to conduct genetic testing, release of genetic results, and when or if to implement experimental therapies. Human prion diseases are both infectious and transmissible; great care is required to balance the needs of the family and individual with both public health needs and strained hospital budgets. It is essential to proactively examine and address the ethical issues involved, as well as to define and in turn provide best standards of care., (Copyright © 2013 Elsevier Ltd. All rights reserved.)