Saturday, October 06, 2018

Evaluation of iatrogenic risk of CJD transmission associated with corneal transplantation

Subject: Evaluation of iatrogenic risk of CJD transmission associated with corneal transplantation

O17 Evaluation of iatrogenic risk of CJD transmission associated with corneal transplantation 

Douet JY. (1), Cassard H. (1), Huor A. (1), Lacroux C. (1), Haïk S. (2), Lugan S. (1), Tillier C. (1), Aron N. (1), Ironside J.W. (3), Andreoletti O. (1) 

(1) UMR INRA-ENVT 1225, Ecole Nationale Vétérinaire de Toulouse, France.(2) Université Pierre et Marie Curie, UMR-S 1127, CNRS UMR 722, Institut du Cerveau et de la Moelle Epinière, G.H. PitiéSalpêtrière, Paris, France.(3) National CJD Research and Surveillance Unit Centre for Clinical Brain Sciences, University of Edinburgh, UK. 

Sporadic Creutzfeldt–Jakob disease (sCJD) has been documented to be accidentally transmitted by contaminated corneal transplants. To date, only one case is considered as definite, while 5 other suspect cases are classified as probable or possible. However, the specific transmission risk associated with this widely-performed transplantation procedure has never been studied. 

In this study, bioassays in transgenic mice expressing the human PrP confirmed the presence of infectivity in the cornea of 2 sCJD patients. Infectivity was also detected in other ocular tissues (optic nerve, retina, vitreous body, choroid and lacrymal gland) from one of these patients. 

Based on these results, we investigated the presence of infectivity in the cornea of different TSE animal models. In conventional mice (RML strain) as well as in sheep (PG127 scrapie), infectivity could only be detected in the corneas collected at the late stage of the disease incubation phase. 

In parallel to these experiments, corneas collected at different stages of the incubation period in infected mice and sheep were grafted into healthy recipients. 

Our results showed that corneas collected during the late asymptomatic phase or in affected animals were able to transmit TSE infectivity. Importantly, after the death of the recipients (up to 2.5 years after surgery) infectivity could still be detected in the grafted cornea. 
These data confirm the potential for sCJD transmission by corneal grafts. They also provide crucial data for the assessing the TSE transmission risk associated with various other ophthalmologic procedures. 



1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8 

*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery. ***

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. 

Laboratory of Central Nervous System Studies, National Institute of 

Neurological Disorders and Stroke, National Institutes of Health, 

Bethesda, MD 20892. 

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them. 

PMID: 8006664 [PubMed - indexed for MEDLINE] 


Case series of Creutzfeldt-Jakob disease in a third-level hospital in Quito

Germaine Eleanor Torres Herrán,Andrés Damián Ortega Herrera,Braulio Martinez Burbano,Marcos Serrano-Dueñas,María Angélica Ortiz Yepez,Raúl Alberto Barrera Madera,Luis Alfredo Masabanda Campaña,Guillermo David Baño Jiménez,Denny Maritza Santos Saltos andEdgar Patricio Correa DíazEmail author

BMC Neurology201818:55


Received: 24 January 2018Accepted: 20 April 2018Published: 27 April 2018

The Correction to this article has been published in BMC Neurology 2018 18:84

Open Peer Review reports

Abstract

Background

Creutzfeldt-Jakob disease is a rare and fatal neurodegenerative disorder that affects mammals and humans. The prevalence of this disease in the United States is 0.5 to 1 per million inhabitants. So far in Ecuador, we do not know what the prevalence or incidence is, and only one case report has been written.

Case presentation

We present a case series of Creutzfeldt-Jakob disease in a third-level hospital in Quito. The average age of symptom onset in our patients was 58.8 years. The male to female ratio was 1:1. Two patients began with cognitive/behavioral symptoms, while 4 patients began with focal neurological signs; 1 case with ataxia, 2 with gait disorders and 1 with vertigo and headache. All of the patients had the clinical features established by the World Health Organization. In addition, the entire cohort was positive for the 14–3-3 protein in cerebrospinal fluid, and had high signal abnormalities in caudate and putamen nucleus in DWI and FLAIR IRM. Only in one case, did we reach a definitive diagnosis through a pathological study. All other cases had a probable diagnosis. In this series of cases, 6 out of 6 patients died. The average time from the onset of the symptoms to death in this cohort was 13 months.

Conclusion

This is the first report of a series of cases of Creutzfeldt-Jakob disease in Quito. Although definitive diagnosis must be histopathological, there are ancillary tests currently available that have allowed us to obtain a diagnosis of the disease.

snip...

Conclusion In conclusion, these are the first case reports of CJD in Ecuador from a third level hospital of Quito. Only in one case, we reach a definitive diagnosis through a pathological study. All other cases had a probable diagnosis. This disease should be considered in individuals older than 50 years of age, with a rapidly progressive dementia associated with myoclonus, visual symptoms, and ataxia accompanied by signs of pyramidal and extrapyramidal dysfunction. Although definitive diagnosis must be histopathological, there are ancillary tests currently available that have allowed us to obtain a diagnosis of the disease.


WEDNESDAY, JULY 04, 2018 

***> CREUTZFELDT-JAKOB DISEASE: GUIDELINES FOR SOCIAL WORKERS IN ENGLAND June 2018


THURSDAY, OCTOBER 04, 2018 

Cervid to human prion transmission 5R01NS088604-04 Update


THURSDAY, SEPTEMBER 27, 2018 

Amydis Awarded Prion Disease Grant from NIH


THURSDAY, OCTOBER 04, 2018 

National Prion Disease Pathology Surveillance Center Cases Examined¹ (September 18, 2018)


FRIDAY, OCTOBER 05, 2018 

More Politicians and Very Young People Struck Down With Creutzfeldt Jakob Disease CJD mad cow type TSE Prion USA


O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations 

Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). 

Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. 

*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, 

***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), 

***is the third potentially zoonotic PD (with BSE and L-type BSE), 

***thus questioning the origin of human sporadic cases. 

We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health. 

=============== 

***thus questioning the origin of human sporadic cases*** 

=============== 

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals. 

============== 
https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf 

***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. 

***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20 


PRION 2016 TOKYO

Saturday, April 23, 2016

SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016

Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online

Taylor & Francis

Prion 2016 Animal Prion Disease Workshop Abstracts

WS-01: Prion diseases in animals and zoonotic potential

Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,

Natalia Fernandez-Borges a. and Alba Marin-Moreno a

"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France

Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion.. Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.

To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.

These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.

Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice. 

Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion. 

These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions. 
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20


why do we not want to do TSE transmission studies on chimpanzees $

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

snip...

R. BRADLEY
https://web.archive.org/web/20170126051158/http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf


Title: Transmission of scrapie prions to primate after an extended silent incubation period) 

*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS. 

*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated. 

*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains. 
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160


***> Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility. <***

Transmission of scrapie prions to primate after an extended silent incubation period 

Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation

Abstract 

Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.

SNIP...

Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.

The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.

We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.

Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.

The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.

Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.

Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.

Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.

Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.

In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free.. Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.


Singeltary on Scrapie and human transmission way back, see;



ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE

here is the latest;

PRION 2018 CONFERENCE
 
Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice 
 
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge). 
 
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. 
 
Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years. After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles. 
 
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate. The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology. Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP. The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD.
 
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
 

READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;
 
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States 
 
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA. 
 
SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD states.
 
AND ANOTHER STUDY;
 
P172 Peripheral Neuropathy in Patients with Prion Disease 
 
Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..
 
IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017, AND included 104 patients.
 
SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%), AND THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.
 
snip...see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below...terry
 
 

Prion 2017 
 
Conference Abstracts CWD 2017 PRION CONFERENCE 
 
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress 
 
Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1 
 
University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen 
 
This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves. Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice. At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation. 
 
PRION 2017 
 
DECIPHERING NEURODEGENERATIVE DISORDERS 
 
Subject: PRION 2017 CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS VIDEO 
 
PRION 2017 
 
CONFERENCE DECIPHERING NEURODEGENERATIVE DISORDERS 
 
*** PRION 2017 CONFERENCE VIDEO 
 
 

TUESDAY, JUNE 13, 2017 
 
PRION 2017 CONFERENCE ABSTRACT 
 
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress 
 
 
 SATURDAY, JULY 29, 2017 
 
Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC 
 
 
just out CDC...see;


Volume 24, Number 8—August 2018

 
Research
 
Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions
 
Marcelo A. BarriaComments to Author , Adriana Libori, Gordon Mitchell, and Mark W. Head Author affiliations: National CJD Research and Surveillance Unit, University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, A. Libori, M.W. Head); National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency, Ottawa, Ontario, Canada (G. Mitchell)
 
M. A. Barria et al.
 
ABSTRACT
 
Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted.

snip...

Discussion

Characterization of the transmission properties of CWD and evaluation of their zoonotic potential are important for public health purposes. Given that CWD affects several members of the family Cervidae, it seems reasonable to consider whether the zoonotic potential of CWD prions could be affected by factors such as CWD strain, cervid species, geographic location, and Prnp–PRNP polymorphic variation. We have previously used an in vitro conversion assay (PMCA) to investigate the susceptibility of the human PrP to conversion to its disease-associated form by several animal prion diseases, including CWD (15,16,22). The sensitivity of our molecular model for the detection of zoonotic conversion depends on the combination of 1) the action of proteinase K to degrade the abundant human PrPC that constitutes the substrate while only N terminally truncating any human PrPres produced and 2) the presence of the 3F4 epitope on human but not cervid PrP. In effect, this degree of sensitivity means that any human PrPres formed during the PMCA reaction can be detected down to the limit of Western blot sensitivity. In contrast, if other antibodies that detect both cervid and human PrP are used, such as 6H4, then newly formed human PrPres must be detected as a measurable increase in PrPres over the amount remaining in the reaction product from the cervid seed. Although best known for the efficient amplification of prions in research and diagnostic contexts, the variation of the PMCA method employed in our study is optimized for the definitive detection of zoonotic reaction products of inherently inefficient conversion reactions conducted across species barriers. By using this system, we previously made and reported the novel observation that elk CWD prions could convert human PrPC from human brain and could also convert recombinant human PrPC expressed in transgenic mice and eukaryotic cell cultures (15).

A previous publication suggested that mule deer PrPSc was unable to convert humanized transgenic substrate in PMCA assays (23) and required a further step of in vitro conditioning in deer substrate PMCA before it was able to cross the deer–human molecular barrier (24). However, prions from other species, such as elk (15) and reindeer affected by CWD, appear to be compatible with the human protein in a single round of amplification (as shown in our study). These observations suggest that different deer species affected by CWD could present differing degrees of the olecular compatibility with the normal form of human PrP.

The contribution of the polymorphism at codon 129 of the human PrP gene has been extensively studied and is recognized as a risk factor for Creutzfeldt-Jakob disease (4). In cervids, the equivalent codon corresponds to the position 132 encoding methionine or leucine. This polymorphism in the elk gene has been shown to play an important role in CWD susceptibility (25,26). We have investigated the effect of this cervid Prnp polymorphism on the conversion of the humanized transgenic substrate according to the variation in the equivalent PRNP codon 129 polymorphism. Interestingly, only the homologs methionine homozygous seed–substrate reactions could readily convert the human PrP, whereas the heterozygous elk PrPSc was unable to do so, even though comparable amounts of PrPres were used to seed the reaction. In addition, we observed only low levels of human PrPres formation in the reactions seeded with the homozygous methionine (132 MM) and the heterozygous (132 ML) seeds incubated with the other 2 human polymorphic substrates (129 MV and 129 VV). The presence of the amino acid leucine at position 132 of the elk Prnp gene has been attributed to a lower degree of prion conversion compared with methionine on the basis of experiments in mice made transgenic for these polymorphic variants (26). Considering the differences observed for the amplification of the homozygous human methionine substrate by the 2 polymorphic elk seeds (MM and ML), reappraisal of the susceptibility of human PrPC by the full range of cervid polymorphic variants affected by CWD would be warranted.

In light of the recent identification of the first cases of CWD in Europe in a free-ranging reindeer (R. tarandus) in Norway (2), we also decided to evaluate the in vitro conversion potential of CWD in 2 experimentally infected reindeer (18). Formation of human PrPres was readily detectable after a single round of PMCA, and in all 3 humanized polymorphic substrates (MM, MV, and VV). This finding suggests that CWD prions from reindeer could be more compatible with human PrPC generally and might therefore present a greater risk for zoonosis than, for example, CWD prions from white-tailed deer. A more comprehensive comparison of CWD in the affected species, coupled with the polymorphic variations in the human and deer PRNP–Prnp genes, in vivo and in vitro, will be required before firm conclusions can be drawn. Analysis of the Prnp sequence of the CWD reindeer in Norway was reported to be identical to the specimens used in our study (2). This finding raises the possibility of a direct comparison of zoonotic potential between CWD acquired in the wild and that produced in a controlled laboratory setting. (Table).

The prion hypothesis proposes that direct molecular interaction between PrPSc and PrPC is necessary for conversion and prion replication. Accordingly, polymorphic variants of the PrP of host and agent might play a role in determining compatibility and potential zoonotic risk. In this study, we have examined the capacity of the human PrPC to support in vitro conversion by elk, white-tailed deer, and reindeer CWD PrPSc. Our data confirm that elk CWD prions can convert the human PrPC, at least in vitro, and show that the homologous PRNP polymorphisms at codon 129 and 132 in humans and cervids affect conversion efficiency. Other species affected by CWD, particularly caribou or reindeer, also seem able to convert the human PrP. It will be important to determine whether other polymorphic variants found in other CWD-affected Cervidae or perhaps other factors (17) exert similar effects on the ability to convert human PrP and thus affect their zoonotic potential.



Dr. Barria is a research scientist working at the National CJD Research and Surveillance Unit, University of Edinburgh. His research has focused on understanding the molecular basis of a group of fatal neurologic disorders called prion diseases.


Acknowledgments

snip...see;
 




Molecular Barriers to Zoonotic Transmission of Prions 
 
Marcelo A. Barria, Aru Balachandran, Masanori Morita, Tetsuyuki Kitamoto, Rona Barron, Jean Manson, Richard Knight, James W. Ironside, and Mark W. Headcorresponding author 
 
snip... 
 
The conversion of human PrPC by CWD brain homogenate in PMCA reactions was less efficient when the amino acid at position 129 was valine rather than methionine. 
 
***Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype. 
 
snip... 
 
However, we can say with confidence that under the conditions used here, none of the animal isolates tested were as efficient as C-type BSE in converting human PrPC, which is reassuring. 
 
***Less reassuring is the finding that there is no absolute barrier to the conversion of human PrPC by CWD prions in a protocol using a single round of PMCA and an entirely human substrate prepared from the target organ of prion diseases, the brain. 


 

ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION 

10. ZOONOTIC, ZOONOSIS, CHRONIC WASTING DISEASE CWD TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION AKA MAD DEER ELK DISEASE IN HUMANS, has it already happened, that should be the question... 

''In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids.'' Scientific opinion on chronic wasting disease (II)

EFSA Panel on Biological Hazards (BIOHAZ) Antonia Ricci Ana Allende Declan Bolton Marianne Chemaly Robert Davies Pablo Salvador Fernández Escámez ... See all authors 

First published: 17 January 2018 https://doi.org/10.2903/j.efsa.2018.5132 ;

also, see; 

8. Even though human TSE‐exposure risk through consumption of game from European cervids can be assumed to be minor, if at all existing, no final conclusion can be drawn due to the overall lack of scientific data. In particular the US data do not clearly exclude the possibility of human (sporadic or familial) TSE development due to consumption of venison. The Working Group thus recognizes a potential risk to consumers if a TSE would be present in European cervids. It might be prudent considering appropriate measures to reduce such a risk, e.g. excluding tissues such as CNS and lymphoid tissues from the human food chain, which would greatly reduce any potential risk for consumers. However, it is stressed that currently, no data regarding a risk of TSE infections from cervid products are available. 

snip... 

The tissue distribution of infectivity in CWD‐infected cervids is now known to extend beyond CNS and lymphoid tissues. While the removal of these specific tissues from the food chain would reduce human dietary exposure to infectivity, exclusion from the food chain of the whole carcass of any infected animal would be required to eliminate human dietary exposure. 
https://efsa.onlinelibrary..wiley.com/doi/full/10.2903/j.efsa.2018.5132

zoonosis zoonotic cervid tse prion cwd to humans, preparing for the storm 

***An alternative to modeling the species barrier is the cell-free conversion assay which points to CWD as the animal prion disease with the greatest zoonotic potential, after (and very much less than) BSE.116*** 
https://www.tandfonline.com/doi/pdf/10.4161/pri.29237
 
To date there is no direct evidence that CWD has been or can be transmitted from animals to humans. 

However, initial findings from a laboratory research project funded by the Alberta Prion Research Institute (APRI) and Alberta Livestock Meat Agency (ALMA), and led by a Canadian Food Inspection Agency (CFIA) scientist indicate that CWD has been transmitted to cynomolgus macaques (the non-human primate species most closely related to humans that may be used in research), through both the intracranial and oral routes of exposure. 

Both infected brain and muscle tissues were found to transmit disease. 

Health Canada’s Health Products and Food Branch (HPFB) was asked to consider the impact of these findings on the Branch’s current position on CWD in health products and foods. 

Summary and Recommendation: 

snip...

Health Portfolio partners were recently made aware of initial findings from a research project led by a CFIA scientist that have demonstrated that cynomolgus macaques can be infected via intracranial exposure and oral gavage with CWD infected muscle. 

These findings suggest that CWD, under specific experimental conditions, has the potential to cross the human species barrier, including by enteral feeding of CWD infected muscle. 
https://www.thetyee.ca/Documents/2017/06/24/Risk-Advisory-Opinion-CWD-2017.pdf


*** WDA 2016 NEW YORK *** 

We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. 

In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. 

***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. 

Student Presentations Session 2 

The species barriers and public health threat of CWD and BSE prions 

Ms. Kristen Davenport1, Dr. Davin Henderson1, Dr. Candace Mathiason1, Dr. Edward Hoover1 1Colorado State University 

Chronic wasting disease (CWD) is spreading rapidly through cervid populations in the USA. Bovine spongiform encephalopathy (BSE, mad cow disease) arose in the 1980s because cattle were fed recycled animal protein. 

These and other prion diseases are caused by abnormal folding of the normal prion protein (PrP) into a disease causing form (PrPd), which is pathogenic to nervous system cells and can cause subsequent PrP to misfold. CWD spreads among cervids very efficiently, but it has not yet infected humans. On the other hand, BSE was spread only when cattle consumed infected bovine or ovine tissue, but did infect humans and other species. 

The objective of this research is to understand the role of PrP structure in cross-species infection by CWD and BSE. To study the propensity of each species’ PrP to be induced to misfold by the presence of PrPd from verious species, we have used an in vitro system that permits detection of PrPd in real-time. 

We measured the conversion efficiency of various combinations of PrPd seeds and PrP substrate combinations. 

We observed the cross-species behavior of CWD and BSE, in addition to feline-adapted CWD and BSE. We found that CWD adapts to a new host more readily than BSE and that human PrP was unexpectedly prone to misfolding by CWD prions. In addition, we investigated the role of specific regions of the bovine, deer and human PrP protein in resistance to conversion by prions from another species. 

***We have concluded that the human protein has a region that confers unusual susceptibility to conversion by CWD prions. CWD is unique among prion diseases in its rapid spread in natural populations. BSE prions are essentially unaltered upon passage to a new species, while CWD adapts to the new species. This adaptation has consequences for surveillance of humans exposed to CWD. Wildlife Disease Risk Communication Research Contributes to Wildlife Trust Administration Exploring perceptions about chronic wasting disease risks among wildlife and agriculture professionals and stakeholders
http://www.wda2016.org/uploads/5/8/6/1/58613359/wda_2016_conference_proceedings_low_res.pdf
 

CDC CWD 2018 TRANSMISSION
https://www.cdc.gov/prions/cwd/transmission.html


TUESDAY, SEPTEMBER 12, 2017 

CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat 
http://chronic-wasting-disease.blogspot.com/2017/09/cdc-now-recommends-strongly-consider.html

SATURDAY, JANUARY 27, 2018 

CDC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE REPORT USA JANUARY 2018
http://chronic-wasting-disease.blogspot.com/2018/01/cdc-chronic-wasting-disease-cwd-tse.html


Subject: CDC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE REPORT USA JANUARY 2018

CHRONIC WASTING DISEASE CWD TSE PRION IS THE USA AND NORTH AMERICA'S MAD COW DISEASE. 

THE USDA INC ET AL WORKED VERY HARD CONCEALING BSE TSE PRION IN CATTLE. they almost succeeded $$$

BUT CWD TSE PRION IN CERVIDS IS A DIFFERENT BEAST, THE COVER UP THERE, USDA INC COULD NOT CONTAIN.

SPORADIC CJD IS 85%+ OF ALL HUMAN TSE PRION DISEASE.

SPORADIC CJD HAS NOW BEEN LINKED TO TYPICAL AND ATYPICAL BSE, SCRAPIE, AND CWD.

SPORADIC/SPONTANEOUS TSE HAS NEVER BEEN PROVEN.

***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
https://www.nature.com/articles/srep11573 

CDC CWD TSE PRION UPDATE USA JANUARY 2018

As of January 2018, CWD in free-ranging deer, elk and/or moose has been reported in at least 22 states in the continental United States, as well as two provinces in Canada. In addition, CWD has been reported in reindeer and moose in Norway, and a small number of imported cases have been reported in South Korea. The disease has also been found in farmed deer and elk. CWD was first identified in captive deer in the late 1960s in Colorado and in wild deer in 1981. By the 1990s, it had been reported in surrounding areas in northern Colorado and southern Wyoming. Since 2000, the area known to be affected by CWD in free-ranging animals has increased to at least 22 states, including states in the Midwest, Southwest, and limited areas on the East Coast.. It is possible that CWD may also occur in other states without strong animal surveillance systems, but that cases haven’t been detected yet. Once CWD is established in an area, the risk can remain for a long time in the environment. The affected areas are likely to continue to expand. Nationwide, the overall occurrence of CWD in free-ranging deer and elk is relatively low. However, in several locations where the disease is established, infection rates may exceed 10 percent (1 in 10), and localized infection rates of more than 25 percent (1 in 4) have been reported. The infection rates among some captive deer can be much higher, with a rate of 79% (nearly 4 in 5) reported from at least one captive herd. As of January 2018, there were 186 counties in 22 states with reported CWD in free-ranging cervids... 

Chronic Wasting Disease Among Free-Ranging Cervids by County, United States, January 2018 

snip.... 
https://www.cdc.gov/prions/cwd/occurrence.html

*** 2017-2018 CWD TSE Prion UPDATE
https://www.cdc.gov/prions/cwd/occurrence.html


*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies. 
http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf

Transmission Studies

Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}....TSS

resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.

snip...
https://web.archive.org/web/20090506002237/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf

Prion Infectivity in Fat of Deer with Chronic Wasting Disease▿ 

Brent Race#, Kimberly Meade-White#, Richard Race and Bruce Chesebro* + Author Affiliations

In mice, prion infectivity was recently detected in fat. Since ruminant fat is consumed by humans and fed to animals, we determined infectivity titers in fat from two CWD-infected deer. Deer fat devoid of muscle contained low levels of CWD infectivity and might be a risk factor for prion infection of other species.
http://jvi.asm.org/content/83/18/9608.full

Prions in Skeletal Muscles of Deer with Chronic Wasting Disease 

Here bioassays in transgenic mice expressing cervid prion protein revealed the presence of infectious prions in skeletal muscles of CWD-infected deer, demonstrating that humans consuming or handling meat from CWD-infected deer are at risk to prion exposure.
http://science.sciencemag.org/content/311/5764/1117.long

*** now, let’s see what the authors said about this casual link, personal communications years ago, and then the latest on the zoonotic potential from CWD to humans from the TOKYO PRION 2016 CONFERENCE.

see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ???? “Our conclusion stating that we found no strong evidence of CWD transmission to humans”

From: TSS (216-119-163-189.ipset45.wt.net)

Subject: CWD aka MAD DEER/ELK TO HUMANS ???

Date: September 30, 2002 at 7:06 am PST

From: "Belay, Ermias"

To: Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"

Sent: Monday, September 30, 2002 9:22 AM

Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Dear Sir/Madam,

In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.. That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

Ermias Belay, M.D. Centers for Disease Control and Prevention

-----Original Message-----

From: Sent: Sunday, September 29, 2002 10:15 AM

To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV

Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS

Thursday, April 03, 2008

A prion disease of cervids: Chronic wasting disease 2008 1: Vet Res. 2008 Apr 3;39(4):41 A prion disease of cervids: Chronic wasting disease Sigurdson CJ.

snip...

*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,

snip... full text ;
http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html

> However, to date, no CWD infections have been reported in people. 

key word here is 'reported'. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can't, and it's as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it's being misdiagnosed as sporadic CJD. ...terry 

*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).*** 
http://www.tandfonline.com/doi/full/10.4161/pri.28124?src=recsys
http://www.tandfonline.com/doi/pdf/10.4161/pri.28124?needAccess=true
https://wwwnc.cdc.gov/eid/article/20/1/13-0858_article


SEE; Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Monday, May 23, 2011

CDC Assesses Potential Human Exposure to Prion Diseases Travel Warning

Public release date: 23-May-2011

Contact: Francesca Costanzo adajmedia@elsevier.com 215-239-3249 Elsevier Health Sciences

CDC assesses potential human exposure to prion diseases Study results reported in the Journal of the American Dietetic Association Philadelphia, PA, May 23, 2011 – Researchers from the Centers for Disease Control and Prevention (CDC) have examined the potential for human exposure to prion diseases, looking at hunting, venison consumption, and travel to areas in which prion diseases have been reported in animals. Three prion diseases in particular – bovine spongiform encephalopathy (BSE or “Mad Cow Disease”), variant Creutzfeldt-Jakob disease (vCJD), and chronic wasting disease (CWD) – were specified in the investigation. The results of this investigation are published in the June issue of the Journal of the American Dietetic Association.

“While prion diseases are rare, they are generally fatal for anyone who becomes infected. More than anything else, the results of this study support the need for continued surveillance of prion diseases,” commented lead investigator Joseph Y. Abrams, MPH, National Center for Emerging and Zoonotic Infectious Diseases, CDC, Atlanta.”But it’s also important that people know the facts about these diseases, especially since this study shows that a good number of people have participated in activities that may expose them to infection-causing agents.”

Although rare, human prion diseases such as CJD may be related to BSE. Prion (proteinaceous infectious particles) diseases are a group of rare brain diseases that affect humans and animals. When a person gets a prion disease, brain function is impaired. This causes memory and personality changes, dementia, and problems with movement. All of these worsen over time. These diseases are invariably fatal. Since these diseases may take years to manifest, knowing the extent of human exposure to possible prion diseases could become important in the event of an outbreak.

CDC investigators evaluated the results of the 2006-2007 population survey conducted by the Foodborne Diseases Active Surveillance Network (FoodNet). This survey collects information on food consumption practices, health outcomes, and demographic characteristics of residents of the participating Emerging Infections Program sites. The survey was conducted in Connecticut, Georgia, Maryland, Minnesota, New Mexico, Oregon, and Tennessee, as well as five counties in the San Francisco Bay area, seven counties in the Greater Denver area, and 34 counties in western and northeastern New York.

Survey participants were asked about behaviors that could be associated with exposure to the agents causing BSE and CWD, including travel to the nine countries considered to be BSE-endemic (United Kingdom, Republic of Ireland, France, Portugal, Switzerland, Italy, the Netherlands, Germany, Spain) and the cumulative length of stay in each of those countries. Respondents were asked if they ever had hunted for deer or elk, and if that hunting had taken place in areas considered to be CWD-endemic (northeastern Colorado, southeastern Wyoming or southwestern Nebraska). They were also asked if they had ever consumed venison, the frequency of consumption, and whether the meat came from the wild.

The proportion of survey respondents who reported travel to at least one of the nine BSE endemic countries since 1980 was 29.5%. Travel to the United Kingdom was reported by 19.4% of respondents, higher than to any other BSE-endemic country. Among those who traveled, the median duration of travel to the United Kingdom (14 days) was longer than that of any other BSE-endemic country. Travelers to the UK were more likely to have spent at least 30 days in the country (24.9%) compared to travelers to any other BSE endemic country. The prevalence and extent of travel to the UK indicate that health concerns in the UK may also become issues for US residents.

The proportion of survey respondents reporting having hunted for deer or elk was 18.5% and 1.2% reported having hunted for deer or elk in CWD-endemic areas. Venison consumption was reported by 67.4% of FoodNet respondents, and 88.6% of those reporting venison consumption had obtained all of their meat from the wild. These findings reinforce the importance of CWD surveillance and control programs for wild deer and elk to reduce human exposure to the CWD agent. Hunters in CWD-endemic areas are advised to take simple precautions such as: avoiding consuming meat from sickly deer or elk, avoiding consuming brain or spinal cord tissues, minimizing the handling of brain and spinal cord tissues, and wearing gloves when field-dressing carcasses.

According to Abrams, “The 2006-2007 FoodNet population survey provides useful information should foodborne prion infection become an increasing public health concern in the future. The data presented describe the prevalence of important behaviors and their associations with demographic characteristics. Surveillance of BSE, CWD, and human prion diseases are critical aspects of addressing the burden of these diseases in animal populations and how that may relate to human health.”

###

The article is “Travel history, hunting, and venison consumption related to prion disease exposure, 2006-2007 FoodNet population survey” by Joseph Y. Abrams, MPH; Ryan A. Maddox, MPH; Alexis R Harvey, MPH; Lawrence B. Schonberger, MD; and Ermias D. Belay, MD. It appears in the Journal of the American Dietetic Association, Volume 111, Issue 6 (June 2011) published by Elsevier.

In an accompanying podcast CDC’s Joseph Y. Abrams discusses travel, hunting, and eating venison in relation to prion diseases. It is available at http://adajournal.org/content/podcast.
http://www.eurekalert.org/pub_releases/2011-05/ehs-cap051811.php


Thursday, May 26, 2011

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Joseph Y. Abrams, MPH, Ryan A. Maddox, MPH , Alexis R. Harvey, MPH , Lawrence B. Schonberger, MD , Ermias D. Belay, MD

Accepted 15 November 2010. Abstract Full Text PDF References .

Abstract

The transmission of bovine spongiform encephalopathy (BSE) to human beings and the spread of chronic wasting disease (CWD) among cervids have prompted concerns about zoonotic transmission of prion diseases. Travel to the United Kingdom and other European countries, hunting for deer or elk, and venison consumption could result in the exposure of US residents to the agents that cause BSE and CWD. The Foodborne Diseases Active Surveillance Network 2006-2007 population survey was used to assess the prevalence of these behaviors among residents of 10 catchment areas across the United States. Of 17,372 survey respondents, 19.4% reported travel to the United Kingdom since 1980, and 29.5% reported travel to any of the nine European countries considered to be BSE-endemic since 1980. The proportion of respondents who had ever hunted deer or elk was 18.5%, and 1.2% had hunted deer or elk in a CWD–endemic area. More than two thirds (67.4%) reported having ever eaten deer or elk meat. Respondents who traveled spent more time in the United Kingdom (median 14 days) than in any other BSE-endemic country. Of the 11,635 respondents who had consumed venison, 59.8% ate venison at most one to two times during their year of highest consumption, and 88.6% had obtained all of their meat from the wild. The survey results were useful in determining the prevalence and frequency of behaviors that could be important factors for foodborne prion transmission.
http://www.adajournal.org/article/S0002-8223(11)00278-1/abstract


PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ; 

Thursday, May 26, 2011

Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey

Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html


NOR IS THE FDA recalling this CWD positive elk meat for the well being of the dead elk ;

Wednesday, March 18, 2009

Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II
http://chronic-wasting-disease.blogspot.com/2009/03/noahs-ark-holding-llc-dawson-mn-recall.html


 Transmissible Spongiform Encephalopathies

Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY
https://web.archive.org/web/20090506001201/http://www.bseinquiry.gov.uk/files/mb/m09a/tab03.pdf


BSE INQUIRY

CJD9/10022

October 1994

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane 

BerksWell Coventry CV7 7BZ

Dear Mr Elmhirst,

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended.. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.
http://web.archive.org/web/20030511010117/http://www.bseinquiry.gov.uk/files/yb/1994/10/00003001.pdf


*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***

*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***

*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). ***

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

snip...

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

snip...

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

snip...

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)

snip...see full report ;

https://web.archive.org/web/20170126073306/http://collections..europarchive..org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1994/08/00004001.pdf


CBC news
 
*** USA sporadic CJD MAD COW DISEASE HAS HUGE PROBLEM Video
 
*** sporadic CJD linked to mad cow disease
 
*** you can see video here and interview with Jeff's Mom, and scientist telling you to test everything and potential risk factors for humans ***
 
 


Infectious agent of sheep scrapie may persist in the environment for at least 16 years

*** Nine of these recurrences occurred 14–21 years after culling

Gudmundur Georgsson,1 Sigurdur Sigurdarson2 and Paul Brown3

Correspondence Gudmundur Georgsson ggeorgs@hi.is

1 Institute for Experimental Pathology, University of Iceland, Keldur v/vesturlandsveg, IS-112 Reykjavı´k, Iceland

2 Laboratory of the Chief Veterinary Officer, Keldur, Iceland

3 Bethesda, Maryland, USA Received 7 March 2006 Accepted 6 August 2006

In 1978, a rigorous programme was implemented to stop the spread of, and subsequently eradicate, sheep scrapie in Iceland. Affected flocks were culled, premises were disinfected and, after 2–3 years, restocked with lambs from scrapie-free areas. Between 1978 and 2004, scrapie recurred on 33 farms. Nine of these recurrences occurred 14–21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded. Of special interest was one farm with a small, completely self-contained flock where scrapie recurred 18 years after culling, 2 years after some lambs had been housed in an old sheephouse that had never been disinfected. Epidemiological investigation established with near certitude that the disease had not been introduced from the outside and it is concluded that the agent may have persisted in the old sheep-house for at least 16 years.

*** Infectious agent of sheep scrapie may persist in the environment for at least 16 years *** 

Gudmundur Georgsson1, Sigurdur Sigurdarson2 and Paul Brown3 



Using in vitro Prion replication for high sensitive detection of prions and prionlike proteins and for understanding mechanisms of transmission. 

Claudio Soto Mitchell Center for Alzheimer's diseases and related Brain disorders, Department of Neurology, University of Texas Medical School at Houston. 

snip...

=========================

***Recently, we have been using PMCA to study the role of environmental prion contamination on the horizontal spreading of TSEs. These experiments have focused on the study of the interaction of prions with plants and environmentally relevant surfaces. Our results show that plants (both leaves and roots) bind tightly to prions present in brain extracts and excreta (urine and feces) and retain even small quantities of PrPSc for long periods of time. Strikingly, ingestion of prion contaminated leaves and roots produced disease with a 100% attack rate and an incubation period not substantially longer than feeding animals directly with scrapie brain homogenate. Furthermore, plants can uptake prions from contaminated soil and transport them to different parts of the plant tissue (stem and leaves). Similarly, prions bind tightly to a variety of environmentally relevant surfaces, including stones, wood, metals, plastic, glass, cement, etc. Prion contaminated surfaces efficiently transmit prion disease when these materials were directly injected into the brain of animals and strikingly when the contaminated surfaces were just placed in the animal cage. These findings demonstrate that environmental materials can efficiently bind infectious prions and act as carriers of infectivity, suggesting that they may play an important role in the horizontal transmission of the disease.

========================

Since its invention 13 years ago, PMCA has helped to answer fundamental questions of prion propagation and has broad applications in research areas including the food industry, blood bank safety and human and veterinary disease diagnosis. 


New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication 


Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production 


Detection of protease-resistant cervid prion protein in water from a CWD-endemic area 


A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing 


Rapid assessment of bovine spongiform encephalopathy prion inactivation by heat treatment in yellow grease produced in the industrial manufacturing process of meat and bone meals 


PPo4-4: 

Survival and Limited Spread of TSE Infectivity after Burial 




TITLE: PATHOLOGICAL FEATURES OF CHRONIC WASTING DISEASE IN REINDEER AND DEMONSTRATION OF HORIZONTAL TRANSMISSION 



 *** DECEMBER 2016 CDC EMERGING INFECTIOUS DISEASE JOURNAL CWD HORIZONTAL TRANSMISSION 


MAD COW USA FLORIDA 2018

WEDNESDAY, SEPTEMBER 26, 2018 

JAVMA In Short Update USDA announces detection of atypical BSE


TUESDAY, SEPTEMBER 4, 2018 

USA CJD, BSE, SCRAPIE, CWD, TSE PRION END OF YEAR REPORTS September 4, 2018



WEDNESDAY, SEPTEMBER 19, 2018 

CHRONIC WASTING DISEASE CWD TSE PRION Detection of a first case in Quebec Canada



SATURDAY, OCTOBER 06, 2018 

Novel Type of Chronic Wasting Disease Detected in European Moose (Alces alces), Norway



TUESDAY, JULY 03, 2018 
 
Chronic Wasting Disease CWD TSE Prion Global Report Update, USA, CANADA, KOREA, NORWAY, FINLAND, Game Farms and Fake news
 
http://chronic-wasting-disease.blogspot.com/2018/07/chronic-wasting-disease-cwd-tse-prion.html

SUNDAY, APRIL 8, 2018 

Transmissible Spongiform Encephalopathy TSE Prion Disease Global Pandemic Urgent Update April 9, 2018


***> NEW TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE (MAD CAMEL DISEASE) IN A NEW SPECIES <***

NEW OUTBREAK OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE IN A NEW SPECIES

Subject: Prion Disease in Dromedary Camels, Algeria

Our identification of this prion disease in a geographically widespread livestock species requires urgent enforcement of surveillance and assessment of the potential risks to human and animal health.



Wednesday, May 30, 2018 

Dromedary camels in northern Africa have a neurodegenerative prion disease that may have originated decades ago


***> IMPORTS AND EXPORTS <***

SEE MASSIVE AMOUNTS OF BANNED ANIMAL PROTEIN AKA MAD COW FEED IN COMMERCE USA DECADES AFTER POST BAN



WEDNESDAY, JULY 11, 2018 

CONFIDENTIAL IN CONFIDENCE SPONGIFORM ENCEPHALOPATHY OF PIGS FDA EMERGENCY REQUEST FOR RULE CHANGE USA Section 21 C.F.R. 589.2000

http://transmissiblespongiformencephalopathy.blogspot.com/2018/07/confidential-in-confidence-spongiform.html



MONDAY, OCTOBER 01, 2018 

Update on Classical and Atypical Scrapie in Sheep and Goats: Review 2018

http://scrapie-usa.blogspot.com/2018/10/update-on-classical-and-atypical.html


MONDAY, OCTOBER 1, 2018 

Review: Update on Classical and Atypical Scrapie in Sheep and Goats

http://nor-98.blogspot.com/2018/10/review-update-on-classical-and-atypical.html

THURSDAY, OCTOBER 04, 2018 

National Prion Disease Pathology Surveillance Center Cases Examined¹ (September 18, 2018)



THURSDAY, MAY 17, 2012 

Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment

I hope and pray that Paul Brown et al rosey outlook is correct, and the end of iatrogenic Creutzfeldt Jakob Disease is truly over, bbut, I have my doubts. ...TSS



2004

-------- Original Message --------
Subject: [CJDVoice] Re: Ophthalmic surgery and Creutzfeldt-Jakob disease
Date: Thu, 01 Jul 2004 21:11:58 -0500
From: "Terry S. Singeltary Sr." 
To: Bovine Spongiform Encephalopathy 


UNCORRECTED PROOF

Sir,

CJD and intraocular surgery

We read with interest the clinical study by Leslie et al,1 in
the May (2003) issue of Eye. The authors eloquently
showed the contamination results before and after the
use of an automated rinsing system. They hypothesized
that the contamination may be the cause of
endophthalmitis found in their unit, but another
observation can be made from their results. The
contaminants noted by the authors included organisms,
lens capsule and cells. The question of whether these
organisms were viable or not is certainly significant but
the finding of lens material may pose a risk of
transmission of Creutzfeldt–Jakob disease (CJD).

CJD is a transmissible human spongioform
encephalopathy characterized by the presence of
abnormal prion protein. Different forms of the disease
exists, for example, sCJD (sporadic), iCJD (following
iatrogenic spread), fCJD (familial), and vCJD (variant,
following the consumption of infected beef). Several
authors have commented on CJD transmission from
ocular transplants, for example, cornea2 or sclera.3
However, intraocular surgical transmission is of concern
due to the sheer volume of cataract surgery performed.
Hogan et al showed a 10-fold increase in prion titres in
the lens in scrapie-infected hamsters once they had
become neurologically symptomatic. In fact, levels in the
lens were similar to levels in the cornea prior to the onset
of neurological symptoms but became significantly
higher than those in the cornea after the onset of
symptoms, retina having the highest titres.4 Intraocular
‘inoculation’ by phacoemulsification and irrigationaspiration
handpieces contaminated by lens material
certainly would provide a route for transmission.

The recent steps taken by the Department of Health in
reviewing sterilizing units probably triggered by the
outbreak of vCJD is certainly welcomed.5 The risk of
intraocular transmission in anterior segment surgery is
probably greater from sCJD than vCJD due to the age of
the patients affected by the respective conditions. Tissue
distribution of prion protein from human eyes has as yet
to show levels of prion in the cornea or lens,6,7 but the
authors concluded that the inability to detect prion
protein in the cornea or lens could not be taken as
evidence for the absence of infectivity in these tissues.7
Since prions adhere strongly to metal surfaces and are
resistant to many sterilization processes,8 the reduction
of contaminants as illustrated by this report in patients
with known or suspected CJD9 and the use of single-use
equipment5 (eg disposable simcoe) will reduce risks of
transmission further.

References

1 Leslie T, Aitken DA, Barrie T, Kirkness CM. Residual debris
as a potential cause of postphacoemulsification
endophthalmitis. Eye 2003; 7: 506–512.

2 Hogan RN, Brown P, Heck E, Cavanagh HD. Risk of prion
disease transmission from ocular donor tissue
transplantation. Cornea 1999; 18: 2–11.

3 Mehta JS, Franks WA. The sclera, the prion, and the
ophthalmologist. Br J Opthalmol 2002; 86: 587–592.

4 Hogan RN, Bowman KA, Baringer JR et al. Replication of
scrapie prions in hamster eyes precedes retinal degeneration.
Ophthalmic Res 1986; 18: 230–235.

5 Tullo AT. CJD and eye surgery-new disease old disease. J Cat
Refract Surg 2003; 29: 629–631.

6 Wadsworth JDF, Joiner S, Hill AF et al. Tissue distribution of
protease resitant prion protein in variant CJD disease using a
highly sensitive immunoblot analysis assay. Lancet 2001; 358:
171–180.

7 Head MW, Northcott V, Rennison K et al. Prion protein
accumulation in eyes of patients with sporadic and variant
CJD. IOVS 2003; 44(1): 342–346.

8 Rutala WA, Weber DJ. Creutzfeldt-Jakob disease:
recommendations for disinfection and sterilization. Clin
Infect Dis 2001; 32: 1348–1356.

9 Weber DJ, Rutala WA. Managing the risk of nosocomial
transmission of prion diseases. Curr Opin Infect Dis 2002; 15:
421–425.

JS Mehta and R Osborne
The Western Eye Hospital
Marylebone Road, London, UK
Correspondence: JS Mehta
9 Sandringham Court
King & Queen Wharf,
Rotherhithe Street,
London SE16 5SQ, UK
Tel: þ44 7980691396
Fax: þ44 8701316622
Eye (2003) 0, 000–000. doi:10.1038/sj.eye.6701401
Journal: IJO Disk used Despatch Date: 31/12/2003
Article: npg_eye_6701401 Pages:1--1 Op: HNM Ed: Naganjana
Q1
Q2
Q3
Eye (2004) 00, 1–1
& 2004 Nature Publishing Group All rights reserved 0950-222X/04 $25.00


CORRESPONDANCE

TSS


Terry S. Singeltary Sr. wrote:

> ######## Bovine Spongiform Encephalopathy 
> #########
>
> April 2004; Vol. 88, No. 4
>
>
>
>
> Series editor: David Taylor
> . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
> . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
> . . . . . . . . . . . . . . .

> Ophthalmic surgery and Creutzfeldt-
> Jakob disease

> P S-Juan, H J T Ward, R De Silva, R S G Knight, R G Will
> . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
> . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
> . . . . . . . . . . .

> Although the evidence does not suggest that contaminated
> ophthalmic instruments represent a risk of onward transmission of
> sporadic CJD, this conclusion should be treated with caution

> The occurrence of variant
> Creutzfeldt-Jakob disease (vCJD)
> and the probable causal link with
> bovine spongiform encephalopathy
> (BSE) in cattle have increased interest
> in the search for possible environmental
> sources of sporadic CJD (sCJD).

> Presumed iatrogenic CJD is rare. Up to
> the year 2000 there had been 267 cases
> reported worldwide: three cases secondary
> to human corneal grafting (one
> confirmed, one probable, and one possible
> case), 114 related to human dura
> mater grafts, 139 related to human
> growth hormone treatment, four related
> to human pituitary gonadotrophin therapy,
> and seven linked to neurosurgical
> procedures or stereotactic EEG electrodes.

> 1 Because of the marked resistance
> of the infectious agent of CJD to
> conventional sterilisation techniques,
> there is concern about the possibility of
> transmission of infection via surgical
> instruments in contact with infected
> tissue, especially in neurosurgery or
> ophthalmic surgery.

> The presence of infection in the eye
> in sCJD was first demonstrated following
> the intracerbral inoculation of
> pooled sCJD eye tissue in non-human
> primates.2 Recently the infectious form
> of prion protein (PrPSc) has been identified
> in the neural retina, optic nerve,
> and in retinal pigmented epithelium
> in variant and sporadic CJD using
> immunohistochemistry or western
> blot,3 4 with comparable levels to those
> found in brain. PrPSc was not detected
> in other ocular tissues. Although this
> suggests that there may be a greater
> risk of contaminating surgical instruments
> in procedures involving the
> posterior segment of the eye, infectivity
> has been demonstrated in animal
> and human cornea,5 and circumstantial
> evidence has implicated corneal
> transplantation as a mechanism of
> transmission of iatrogenic CJD.6 Experimental
> infection has been achieved
> following conjunctival installation of
> scrapie infectivity in mice7 and by
> inoculation of an adapted agent into
> the anterior chamber of the eye in
> guinea pigs.8

> Recently it has been shown that the
> experimental transmission of metallic
> suface bound prions is highly efficient.9
> Steel wires in contact with the brain of
> pre-symptomatic mice needed only
> 5 minutes to acquire an infectious load
> equivalent to the injection of a 1%
> homogenate of brain. Infected wires
> were inserted transiently into the brains
> of healthy mice and only 30 minutes of
> exposure was sufficient to result in
> infection. The same wires remained
> infective when reintroduced into
> another set of healthy mice. Although,
> to our knowledge, there have been no
> documented cases of CJD secondary to
> ophthalmic surgery other than corneal
> transplantation, there is a possibility
> that ophthalmic surgery might be a risk
> procedure for the accidental iatrogenic
> transmission of CJD.

> Precautions to minimise the risks of
> iatrogenic transmission of CJD are vital
> and the Department of Health has
> established an incidents panel to provide
> advice in cases of all forms of
> human prion diseases in which there is
> the possibility for cross infection.
> However, an important question is
> whether the concerns raised by experimental
> work translate into an actual
> risk in the clinical setting. This commentary
> reviews the data on ophthalmic
> surgery in sCJD and vCJD from the
> archives of the UK National CJD
> Surveillance Unit from 1990 to 2002,
> including information on both sCJD and
> vCJD.

> We analysed the surgical history of
> sCJD and vCJD cases with specific
> reference to ophthalmic surgery. Cases
> of CJD were identified in the current
> prospective UK national surveillance
> project (1990-October 2002) by direct
> notification or from death certificates,10
> and were classified as definite, probable,
> or possible cases of sCJD or vCJD
> according to published diagnostic criteria.
> Only definite or probable cases
> were included in this analysis. All cases
> with a history of ophthalmic surgery
> were identified from the database,
> which has a specific code for this type
> of surgery. Information on past ophthalmic
> surgery was obtained from relatives,
> general practitioner records, and/or
> copies of case notes. Case files were
> examined to identify the type of surgery,
> date of surgery, and hospital in which
> the surgery had taken place. In cases in
> which the surgery was carried out after
> the onset of clinical symptoms of CJD
> detailed information on the clinical
> course was extracted.

> The frequency of a history of eye
> surgery in sCJD and vCJD was compared
> with data on the frequency of past
> eye surgery in age and sex matched
> control groups. During the period of the
> study the case-control study has
> evolved. Between 1990 and 1998 a
> single hospital control was obtained for
> the sCJD cases and from 1999 2002 a
> single community based control was
> identified. From 1996 2002 a single
> hospital control was obtained for vCJD
> cases and since 1998 attempts have been
> made to obtain four community based
> controls per case of vCJD. Because of the
> limited numbers of controls and the
> infrequency of past eye surgery this
> study reports on unmatched comparisons
> of the frequency of past eye
> surgery.

> Fifty eight cases of sCJD (11%) out of
> 510 with information available had a
> history of intraocular surgery, with an
> average of 1.34 interventions per
> patient. The types of operation (n=78)
> in the total of 58 cases having undergone
> any form of ocular surgery are
> listed in table 1 and the years of
> operation in figure 1. Ten cases of
> sCJD underwent eye surgery during
> Table 1 Types of operation on cases of sporadic CJD
> Number of operations
> on sCJD cases
> Number of
> operations on
> hospital controls
> Number of operations
> on community controls
> (n = 78) (n = 39) (n = 20)
> Intraocular surgery* 55 (70%) 29 (74%) 17 (85%)
> Extraocular surgery 17 (22%) 6 (16%) 3 (15%)
> Laser therapy 4 (5%) 2 (5%)
> Information not available 2 (3%) 2 (5%)
> *Cataract, trauma, and glaucoma.
> 446 COMMENTARY
> the prodromal (within 3 months of
> onset) or early symptomatic phase of
> the disease, the majority cataract operations.
> Four out of these 10 patients had
> the Heidenhain variant of sCJD, with
> visual onset and early development of
> cortical blindness (table 2). Figure 2
> shows the time interval between last eye
> surgery and the onset of symtoms in
> sCJD patients.

> The frequency of past eye surgery was
> compared with the control groups in
> sCJD (table 3) and vCJD. In the hospital
> control group for sCJD, 31 (14%) out of
> 226 had a history of ophthalmic surgery,
> with an average of 1.26 procedures per
> patient and in the community control
> group for sCJD 14 (13%) out of 106,
> with an average of 1.43 procedures per
> patient. Eight patients with vCJD (6%)
> out of 125 with information available
> had a history of eye surgery and all were
> squint corrections in childhood, with
> the exception of one case with a history
> of open surgery for retinal detachment
> carried out 15, 17, and 20 months before
> the development of symptoms (this case
> predated the establishment of the CJD
> incidents panel). In the hospital control
> group for vCJD (15%) 10 out of 67 had a
> history of ophthalmic surgery and in the
> community control group for vCJD five
> (3%) out of 155 had had eye surgery.
> There were no significant (at the 5%
> level) differences between the frequencies
> of past eye surgery in the cases and
> any of the control groups.
> Details of the year and hospital of
> each surgical procedure were listed and
> in the great majority there was no
> temporal or geographic link between
> operations. A group of six cases of sCJD
> had been operated on in one hospital
> and in two pairs of cases the procedures
> had been carried out in the same year.
> Inquiry about the specific dates of these
> procedures, however, indicated that the
> operations had been carried out months
> apart.

> The aim of this article is to document
> the frequency of past eye surgery in CJD
> and to determine whether there is
> evidence of transmission of CJD
> through contaminated ophthalmic
> instruments. About 10% of cases of
> sCJD have a history of eye surgery, of
> which about 70% involved open surgery
> on the anterior chamber of the eye. In
> the great majority of cases the surgical
> instruments were reused on subsequent
> patients, usually because CJD developed
> years after the original procedure.

> Despite this, the evidence in this paper
> does not suggest that there is onward
> iatrogenic transmission of sCJD through
> eye surgery, a finding consistent with
> some previous studies.11 12
> An important question is whether
> cases of CJD caused by this type of

> Figure 1 Year of eye surgery in sCJD.
> Table 2 sCJD patients with ophthalmic surgery after clinical onset
> Case Date of surgery Intervention
> Heidenhain
> variant Diagnosis
> 1 1992 Cataract Definite
> 2 1992 Laser therapy * Definite
> 3 1992 Cataract * Definite
> 4 1993 Cataract Definite
> 5 1996 Cataract Definite
> 6 1998 Dacryocystorhinostomy Definite
> 7 1998 Cataract Definite
> 8 1999 Cataract * Definite
> 9 1999 Laser therapy * Definite
> 10 2000 Cataract Definite
> *Heidenhain variant: cases with isolated cortical visual symptoms at 
> onset.

> Figure 2 Interval between last eye surgery and onset of symptoms in sCJD
> (n = 54).

> Table 3 Past ophthalmic surgery in sCJD compared with control groups
> Cases Hospital controls Community controls
> (n = 510) (n = 226) (n = 106)
> Patients with eye operations 58 (11%) 31 (14%) 14 (13%)
> Total number of operations 78 39 20
> Average per patient 1.34 1.26 1.43
> COMMENTARY 447

> transmission would be identified by this
> study. The clinicopathological features
> and incubation period of iatrogenic CJD
> vary according to the route of transmission
> with, for example, a cerebellar
> syndrome and only limited cognitive
> impairment in human growth hormone
> related CJD. In CJD caused by corneal
> transplantation the clinical and pathological
> phenotype is similar to sCJD and
> the incubation periods in the three cases
> reported to date were 15 months,
> 18 months, and 30 years.6 13 The surveillance
> system for CJD in the United
> Kingdom is efficient at identifying cases
> as judged by annual incidence rates of
> sCJD of around one case per million,
> and it is likely that cases with a typical
> phenotype would be identified. The
> period of observation of CJD from 1990
> to 2002, with additional information
> from 1980 9, suggests that there is the
> potential to identify case to case transmission
> through past eye surgery, with
> the assumption that the incubation
> period of such cases would be months
> or years rather than decades. It is,
> however, important to emphasise that
> a significant proportion of the eye
> operations were carried out relatively
> recently and, if the incubation period
> were extended, onward transmission
> may not have been identified by this
> study.

> Evidence of transmission of sCJD
> through contaminated neurosurgical
> instruments rests on the close temporal
> relation between operations carried out
> on CJD cases and unaffected individuals
> who subsequently developed CJD.14 15
> An analysis of the dates and sites of
> eye operations in cases of sCJD in this
> study showed no such relation. The
> elegant experiments by Weismann et
> al9 raise the possibility that surgical
> instruments contaminated during neurosurgery
> might pose a significant risk
> of iatrogenic transmission. In this context
> it is of interest that a number of
> cases of sporadic (and iatrogenic) CJD
> have undergone brain surgery (12/400
> cases in the European study), but there
> is no evidence from case-control studies
> that previous neurosurgery increases the
> risk of developing sporadic CJD. This is
> despite the fact that potentially contaminated
> neurosurgical instruments
> have inadvertently been reused on other
> patients on a number of occasions.

> The 10 cases of sCJD undergoing eye
> surgery in the early clinical stages of the
> illness may represent the greatest risk of
> onward transmission of infection,
> because there are probably higher levels
> of infection in the eye late in the
> incubation period as a result of centrifugal
> spread of infection along the optic
> nerve.4 The diagnosis of sCJD can be
> very difficult in the early stages of the
> clinical illness and this is particularly
> true of cases with isolated cortical visual
> symptoms (the Heidenhain variant of
> sCJD), which affected four of these 10
> cases. The presence of confusion, memory
> impairment, or other neurological
> signs may raise the suspicion of a
> neurodegenerative disorder.

> The data on vCJD are limited and the
> period of observation is shorter than in
> sCJD. Although there is currently no
> evidence of transmission of vCJD
> through contaminated ophthalmic
> instruments, this possibility cannot be
> excluded, not least because the incubation
> period in vCJD is unknown.

> Furthermore, in vCJD the presence of
> prion protein (PrP) immunostaining in
> systemic lymphoreticular tissues suggests
> that the risk from contaminated
> surgical instruments may be greater
> than in sCJD, in which these tissues
> do not stain for PrP, using comparable
> methods.

> The data from our case-control study
> show no significant risk related to a
> history of eye surgery in sCJD in
> comparison with two control groups.
> The methodology of the case-control
> study in our analysis is not ideal. There
> is a deficit in the numbers of controls in
> comparison with the numbers of cases
> and an unmatched analysis was undertaken.
> The results of our study are,
> however, consistent with the results of
> a previous case-control study in
> Europe,12 but contrast with the results
> of an Australian study in which previous
> cataract/eye surgery was associated with
> a more than sixfold increase in the risk
> of sCJD.16 The studies used different
> types of control group, the European
> study hospital controls and the
> Australian study community controls.
> However, in a reanalysis of the
> European data using a community control
> group, eye surgery was again found
> not to increase the risk of sporadic
> CJD.11 The disparity in outcome in the
> two studies relates primarily to the
> frequency of previous eye surgery in
> the control groups (European studies
> 34/406, 8% , 37/325, 11%: Australian 24/
> 784, 3%) rather than the cases
> (European studies 33/401, 8%, 37/328,
> 11%: Australian 24/241, 10%). Although
> this type of study cannot exclude the
> possibility of rare instances of iatrogenic
> transmission of CJD through eye
> surgery, the balance of evidence does
> not support the hypothesis that exposure
> to potentially contaminated
> ophthalmic instruments has, hitherto,
> been associated with the risk of developing
> CJD.

> Although the evidence in this paper
> does not suggest that contaminated
> ophthalmic instruments represent a
> risk of onward transmission of sporadic
> CJD, this conclusion should be treated
> with caution. The eye contains significant
> levels of infection in sCJD and
> vCJD, and even limited exposures can
> result in the iatrogenic transmission of
> CJD.17

> This paper confirms that ophthalmologists
> may be involved in treating
> patients in the early stages of CJD and
> it is essential to follow current guidelines
> in relation to surgical, including
> ophthalmic and neurosurgical, instruments
> used in suspect cases of CJD of all
> types.18 Such instruments should be
> destroyed or quarantined until a definitive
> diagnosis is available and the
> development of single use devices and
> instruments in eye surgery has been
> advocated,19 provided these do not prejudice
> clinical outcome. All cases of
> suspect CJD should be reported to the
> local consultant in communicable disease
> control in order that appropriate
> measures to protect public health
> are instituted, including a review of
> previous surgery. Advice on specific
> cases which raise concern is available
> fromthe CJD incidents panel (www.doh.
> gov.uk/cjd/incidentspanel.htm), which
> has published a consultation document

> ACKNOWLEDGEMENTS
> We would like to thank Dr JF Geddes and
> Miss Gillian Adams, FRCS, for their help in
> confirming some of the clinical details. PS-J
> was supported by the postMIR grant
> Wenceslao Lopez Albo from the IFIMAV
> Institute of the Fundacio´n Pu´blica Marque´s
> de Valdecilla. The National CJD Surveillance
> Unit is funded by the Department of
> Health and the Scottish Executive Health
> Department.
> Br J Ophthalmol 2004;88:446 449.
> doi: 10.1136/bjo.2003.028373
> Authors affiliations
> . . . . . . . . . . . . . . . . . . . . . .
> P S-Juan, H J T Ward, R S G Knight, R G Will,
> The National CJD Surveillance Unit, Western
> General Hospital, Edinburgh EH4 2XU, UK
> R De Silva, Oldchurch Hospital, Romford, UK
> Correspondence to: R G Will, The National CJD
> Surveillance Unit, Western General Hospital,
> Edinburgh EH4 2XU, UK; r.g.will@ed.ac.uk
> Accepted for publication 19 August 2003
> REFERENCES
> 1 Brown P, Preece M, Brandel JP, et al. Creutzfeldt-
> Jakob disease at the millennium. Neurology
> 2000;55:1075 81.
> 2 Brown P, Gibbs CJ, Rodgers-Johnson P, et al.
> Human spongiform encephalopathy: The
> National Institutes of Health Series of 300 cases of
> experimentally transmitted disease. Ann Neurol
> 1994;35:513 29.
> 3 Wadsworth JD, Joiner S, Hill AF, et al. Tissue
> distribution of protease resistant prion protein in
> variant Creutzfeldt-Jakob disease using a highly
> sensitive immunoblotting assay. Lancet
> 2001;358:171 80.
> 448 COMMENTARY
> 4 Head MW, Northcott V, Rennison K, et al. Prion
> protein accumulation in eyes of patients with
> sporadic and variant Creutzfeldt-Jakob disease.
> Invest Ophthalmol Vis Sci 2002;44:342 6.
> 5 Lueck CJ, McIlwaine GG, Zeidler M. Creutzfeldt-
> Jakob disease and the eye. I Background and
> patient management. Eye 2000;14:263 90.
> 6 Hogan RN, Brown P, Heck E, et al. Risk of prion
> disease transmission from ocular donor tissue
> transplantation. Cornea 1999;18:2 11.
> 7 Scott JR, Foster JD, Fraser H. Conjunctival
> instillation of scrapie in mice can produce disease.
> Vet Microbiol 1993;34:305 9.
> 8 Manuelidis EE, Angelo JN, Gorgacz EJ, et al.
> Experimental Creutzfeldt-Jakob disease
> transmitted via the eye with infected cornea.
> N Eng J Med 1977;296:1334 6.
> 9 Weissmann C, Enari M, Klohn P-C, et al.
> Transmission of prions. J Infect Dis
> 2002;186:S157 65.
> 10 Cousens SN, Zeidler M, Esmonde TF, et al.
> Sporadic Creutzfeldt-Jakob disease in the United
> Kingdom: analysis of epidemiological
> surveillance data for 1970 76. BMJ
> 1997;315:389 95.
> 11 Ward HJT, Everington D, Croes EA, et al.
> Sporadic Creutzfeldt-Jakob disease and surgery:
> a case control study using community controls.
> Neurology 2002;59:543 8.
> 12 Van Duijn CM, Delasnerie-LaupreÆtre N,
> Masullo C, et al. Case control study of risk factors
> of Creutzfeldt-Jakob disease in Europe during
> 1993 95. Lancet 1998;351:1081 5.
> 13 Heckmann JG, Lang CJG, Petruch F, et al.
> Transmission of Creutzfeldt-Jakob disease via
> corneal transplant. J Neurol Neurosurg Psychiatry
> 1997;63:388 90.
> 14 Will RG, Matthews WB. Evidence for case-tocase-
> transmission of Creutzfeldt-Jakob disease.
> J Neurol Neurosurg Psychiatry 1982;45:235 8.
> 15 Foncin JF, Gaches J, Cathala F, et al. Transmission
> iatrogene interhumaine possible de maladie
> de Creutzfeldt-Jakob avec atteinte des grains de
> cervelet. Rev Neurol (Paris) 1980;136:280.
> 16 Collins S, Law MG, Fletcher A, et al. Surgical
> treatment and risk of sporadic Creutzfeldt-Jakob
> disease: a case-control study. Lancet
> 1999;353:693 7.
> 17 Croes EA, Roks CMAA, Jansen GH, et al.
> Creutzfeldt-Jakob disease 38 years after
> diagnostic use of human growth hormone.
> J Neurol Neurosurg Psychiatry 2002;72:792 3.
> 18 Department of Health. Transmissible spongiform
> encephalopathy agents: safe working and the
> prevention of infection: publication of revised
> ACDP/SEAC guidance. London: DoH, June 2003
> 19 Tullo A. Creutzfeldt-Jakob disease and eye
> surgery new disease, old disease. J Cataract
> Refract Surg 2003;29:629 31.
> The lighter
> side................................................................................... 
>
> EMichael Balis.
> COMMENTARY 449
> =====================
>

> Subject: RE-The Eyes Have It (cjd) and they could be stealing them from
> your loved one... "pay back time"
> Date: Sat, 16 Sep 2000 10:04:26 -0700
> From: "Terry S. Singeltary Sr."
> Reply-To: Bovine Spongiform Encephalopathy
> To: BSE-L
>
> Greetings List Members,
>
> I hate to keep kicking a madcow, but this still is very disturbing
> to me. Not only for the recipient of the cornea's, but as well, for
> the people whom would be operated on, using the same tools that
> were used to put those stolen cornea's in the recipient with.
> No history of this donor or his family (re-ffi), or anything
> would be known, using stolen organs and or tissue's. I just think
> this is not only wrong, but very dangerous to a great many other
> people, as this is one of the most infectious tissues of TSE's. It seems
> that this practice of stealing organ/tissue happens more than we think.
> Anyway, the family of the victim which had their cornea's stolen, are
> now suing. In the example I used with my Mother, if 3 months before, she
> would have been in a catastrophic accident (car wreck, whatever), no
> autopsy (for whatever reason), no family (for whatever reason), she lay
> in the morgue, and after 4 hours, they come steal the cornea's, lot of
> people could have been infected, just because of lack of medical history
> of donor/family. It may be hypothetical, but very real. We need to stop
> the spread of this disease.
>
> kind regards,
> Terry S. Singeltary Sr., Bacliff, Texas USA
> ===========================================
>
> Previous story--
>
> Cadaver corneal transplants -- without family permission...
> ===============================================
>
> Sept. 15, 2000, 11:39PM
>
> Slain woman's family sues over
> missing eyes
>
> By BILL MURPHY
> Copyright 2000 Houston Chronicle
>
> The family of a woman who was stabbed to death last year has
> filed a lawsuit accusing the Lions Eye Bank of Houston of
> removing the woman's eyes without permission and inserting
> plastic discs in their place.
>
> Daisy Diaz's relatives were horrified when they saw her body
> and noticed her eyes were missing, said their lawyer, Duncan
> Neblett III.
>
> "They're a Catholic family," Neblett said. "They have strong
> beliefs about the body and burial. They were really upset by
> this."
>
> Dorey Zidrow, the eye bank's spokeswoman, said she could
> not specifically discuss the Diaz case because it was in litigation.
> But Zidrow said a state law allows doctors to remove corneas
> -- the dime-sized lens near the eye's surface -- from a corpse
> without the family's permission.
>
> The eye bank's usual procedure calls for removing the corneas,
> Zidrow said, but not the entire eyes.
>
> "There are an awful lot of people who benefit from this program
> in the state of Texas," she said.
>
> Diaz, 25, was stabbed to death in her apartment in the 400
> block of Thornton in October. Her brother-in-law, 30-year-old
> Raudel Quiroz, is charged in the killing but has not been caught.
>
> Neblett said authorities have told him Quiroz may have returned
> to his native Guatemala.
>
> Neither Diaz nor her family had given permission to donate any
> of her organs, Neblett said.
>
> Although state law allows corneas to be removed from corpses
> without first gaining the family's permission, they cannot be
> removed over the family's stated objection.
>
> The eye bank is located at, and staffed by, the Baylor College
> of Medicine, and receives part of its funding from the Lions
> Club.
>
> The Diaz lawsuit is the second such suit to be filed against the
> eye bank in recent years.
>
> The family of Levi Perry Jr., a Houston teacher shot to death in
> MacGregor Park in 1994, also alleged in their suit that Perry's
> eyes were removed. The family was awarded $345,000 from
> the eye bank in April 1999.
>
> ==========================================================
>
> THE LEGALITY OF STEALING ORGAN/TISSUE...
>
> TEXAS STATUTES
>
> Sec. 693.012. Removal of Corneal Tissue Permitted Under Certain
> Circumstances.
>
> snip...
>
> Search 1999 Legislation for: 693.014
>
> [[[as you can see, they knew it was wrong when they wrote the laws. or
> they would not have covered the rear-ends so well...TSS]]]
> ---------------------------------------------------------
> thanks again,
> kind regards,
> Terry S. Singeltary Sr.
>
> 
>
> a bit of history;
>
> The Eyes have it/CJD * and they could be stealing them from YOUR loved
> one, hence the
> spread of CJD (aka MADCOW DISEASE) will spread...
>
> 1
> 
>
> 2
> 
>
> 3
> 
>
>
>
> Testimony of Bess Believeaux, Lions Eye Bank of Central Texas
> (Submission to the Jan. 18/19 meeting of the
> TSE Advisory Committee)
>
>
> TSS Submission to the same Committee;
>
> Tissue Banks International (TBI), Gerald J Cole
>
> re-use contact lenses
> 
>
> TSS
>
> ############
>

END...TSS...FLOUNDER...GALVESTON BAY...on the bottom...---...

posted by Terry S. Singeltary Sr. at 12:33 PM