Thursday, August 13, 2015

Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years

Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years

 

Peter Rudge, Zane Jaumuktane, Peter Adlard, Nina Bjurstrom, Diana Caine, Jessica Lowe, Penny Norsworthy, Holger Hummerich, Ron Druyeh, Jonathan D. F. Wadsworth, Sebastian Brandner, Harpreet Hyare, Simon Mead, and John Collinge

 

Brain published 11 August 2015, 10.1093/brain/awv235

 

Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years

 

(CC) Peter Rudge, Zane Jaumuktane, Peter Adlard, Nina Bjurstrom, Diana Caine, Jessica Lowe, Penny Norsworthy, Holger Hummerich, Ron Druyeh, Jonathan D. F. Wadsworth, Sebastian Brandner, Harpreet Hyare, Simon Mead, John Collinge DOI: http://dx.doi.org/10.1093/brain/awv235 First published online: 12 August 2015 Summary Patients with iatrogenic Creutzfeldt-Jakob disease due to administration of cadaver-sourced growth hormone during childhood are still being seen in the UK 30 years after cessation of this treatment. Of the 77 patients who have developed iatrogenic Creutzfeldt-Jakob disease, 56 have been genotyped. There has been a marked change in genotype profile at polymorphic codon 129 of the prion protein gene (PRNP) from predominantly valine homozygous to a mixed picture of methionine homozygous and methionine-valine heterozygous over time. The incubation period of iatrogenic Creutzfeldt-Jakob disease is significantly different between all three genotypes. This experience is a striking contrast with that in France and the USA, which may relate to contamination of different growth hormone batches with different strains of human prions. We describe the clinical, imaging, molecular and autopsy features in 22 of 24 patients who have developed iatrogenic Creutzfeldt-Jakob disease in the UK since 2008. Mean age at onset of symptoms was 42.7 years. Gait ataxia and lower limb dysaesthesiae were the most frequent presenting symptoms. All had cerebellar signs, and the majority had myoclonus and lower limb pyramidal signs, with relatively preserved cognitive function, when first seen. There was a progressive decline in neurological and cognitive function leading to death after 5–32 (mean 14) months. Despite incubation periods approaching 40 years, the clinical duration in methionine homozygote patients appeared to be shorter than that seen in heterozygote patients. MRI showed restricted diffusion in the basal ganglia, thalamus, hippocampus, frontal and the paracentral motor cortex and cerebellar vermis. The electroencephalogram was abnormal in 15 patients and cerebrospinal fluid 14-3-3 protein was positive in half the patients. Neuropathological examination was conducted in nine patients. All but one showed synaptic prion deposition with numerous kuru type plaques in the basal ganglia, anterior frontal and parietal cortex, thalamus, basal ganglia and cerebellum. The patient with the shortest clinical duration had an atypical synaptic deposition of abnormal prion protein and no kuru plaques. Taken together, these data provide a remarkable example of the interplay between the strain of the pathogen and host prion protein genotype. Based on extensive modelling of human prion transmission barriers in transgenic mice expressing human prion protein on a mouse prion protein null background, the temporal distribution of codon 129 genotypes within the cohort of patients with iatrogenic Creutzfeldt-Jakob disease in the UK suggests that there was a point source of infecting prion contamination of growth hormone derived from a patient with Creutzfeldt-Jakob disease expressing prion protein valine 129.

 

snip...

 

Discussion

 

This study, covering the period from 2000–14, shows that iatrogenic CJD due to cadaver-sourced pituitary growth hormone, a treatment that was discontinued in 1985 in the UK, continues to occur in the UK at a frequency of 0–6 cases per annum. Incubation periods are now extraordinarily long, with estimates ranging from 18–40 years, the uncertainty based on clinical onsets and lengths of treatment with potentially infected batches. In this paper we have reviewed the clinical features, progression, imaging abnormalities, prion protein genotype, PrPSc type by western blot and preliminary neuropathology data.

 

Clinical features and imaging correlations Typically patients with growth hormone induced iatrogenic CJD present with gait ataxia, cerebellar dysarthria and lower limb pain with cognitive function much less affected. Later sleep disturbance, cognitive decline and pyramidal signs with weakness in the lower limbs develops. Ultimately, the patient enters an akinetic mute state typical of all types of CJD with death at 4–32 (mean 16.0) months after the initial presentation. There are several points of special interest in this clinical presentation.

 

First, gait ataxia, with much less limb ataxia, especially in the upper limbs, is typical of superior cerebellar vermis damage. The MRI and pathological examination of the cerebellum demonstrated extensive damage of the vermis with lesser involvement of the cerebellar hemispheres consistent with these clinical findings. Interestingly, in addition to gait ataxia, two of the patients presented with abnormal visual input imbalance characterized by unsteadiness induced by moving stimuli (waves when paddling and looking at moving water) suggesting abnormal visual vestibular interaction partly dependent on cerebellar pathways.

 

Second, pain in the lower limbs was of a quality suggesting abnormal spino-thalamic function and MRI confirmed a diffuse abnormality of the thalamus which, although maximal medially, did extend laterally to the ventro-posterior components, part of the pain and thermal pathways. Of note is the similarity of this pain to that experienced by many patients with variant CJD and kuru, which are also acquired prion diseases associated with peripheral infection with prions where thalamic involvement, especially posteriorly, occurs. However, a contribution of the more peripheral components of the spino-thalamic system cannot be excluded.

 

Third, later in the course of the disease cognitive dysfunction with prominent memory decline emerged. The extensive involvement of many areas of the deep nuclei, thalamus and cortex could explain this, but of note is the prominent involvement of the hippocampus on MRI and pathologically. This, together with the thalamic changes, is an adequate explanation of the amnesia. Thalamic involvement would also explain the sleep disturbance similar to that occurring in fatal familial insomnia (FFI) and frequently seen in sporadic CJD.

 

Finally, weakness in the lower limbs due to pyramidal involvement correlated with cortical ribboning involving the dorsal and medial motor strip demonstrated on MRI in most patients. Such involvement of the motor cortex is rare in other forms of prion disease. More pronounced involvement of the motor cortex and parietal lobe when compared with the anterior frontal or occipital cortex was also confirmed morphologically with extensive micro-vacuolar change and intense deposition of synaptic abnormal prion protein.

 

Neuropathology A detailed quantitative analysis of the pathology in the nine autopsied cases will be the subject of a separate communication. However, a striking feature was the presence of PrP plaques in all but one case. This latter non-plaque case suggests that the different pathological appearances might be caused by different prion strains. Similarly, iatrogenic CJD due to dural grafts, a condition particularly prevalent in Japan, may show two distinct pathologies, plaque-type and non-plaque-type, which have been linked with differing transmission properties in transgenic mice (Kobayashi et al., 2014). It is possible that future studies using material from the original batches of pituitary-derived growth hormone and transgenic mice could clarify the pathogenesis of the disease in our cases and comparison with the literature on dural graft iatrogenic CJD.

 

PRNP codon 129 polymorphism determines incubation time A remarkable feature of iatrogenic CJD cases in the UK is the distribution of the codon 129 polymorphism. An excess of VV homozygotes was reported in early UK cases and then thought to be a marker of susceptibility (Collinge et al., 1991). MV heterozygosity was reported to confer relative resistance to sporadic CJD (Palmer et al., 1991). In the initial study of 27 UK patients 52% were homozygous for valine and only 4% (one case) was homozygous for methionine; the remainder were heterozygotes. This contrasts with the French experience in 77 patients where 48% were homozygous for methionine and 22% homozygous for valine (Brandel et al., 2003). Similar proportions were also found in the few cases reported from the USA (Brown et al., 2012). Furthermore in sporadic CJD, kuru and variant CJD, methionine homozygosity predominates. This is thought to result from the relative resistance afforded by heterozygosity at polymorphic PrP residue 129 and from conformational selection whereby different prion strains are preferentially propagated by prion proteins of different primary sequence (Collinge, 1999; Collinge and Clarke, 2007). For example the bovine spongiform encephalopathy-related prion strain causing variant CJD appears only to be compatible with methionine 129 human PrP (Wadsworth et al., 2004).

 

One of the new findings of our study of UK patients is that there has been a change in the distribution of the 129 polymorphism in the past 12 years. The VV genotype has now greatly decreased and MM genotype increased while the frequency of heterozygotes has remained relatively constant. There are similarities and differences from the studies of kuru (Cervenakova et al., 1999; Collinge et al., 2006; Mead et al., 2009b). In kuru both homozygous genotypes predominated in young cases with presumably a shorter incubation time, but in later and older cases heterozygotes occurred more frequently.

 

A possible explanation for these superficially contradictory distributions of codon 129 in different outbreaks could be the compatibility of host genotype and strain of the infecting prion, in keeping with the conformational selection model of prion transmission (Collinge, 1999; Collinge and Clarke, 2007). This model suggests that transmission is facilitated, with shorter incubation times, if the host prion protein can readily adopt the preferred conformation associated with the strain of the infecting prion. In the case of the UK, it is likely that one particular preparation (Hartree modified Wilhelmi preparation) was responsible for the outbreak as all patients to date received this preparation.

 

Swerdlow et al. (2003) estimated that ∼400 000 pituitaries were harvested for growth hormone production, but even this may be an underestimate. Attempts were made to exclude patients who had neurological diseases but protocols for harvesting were not strictly monitored (Swerdlow et al., 2003). It is likely that some of these pituitary glands were sourced from cases with CJD; in the 1970s, the time when the majority of pituitary sourced growth hormone was obtained, it is estimated from UK mortality data that 1 in 7000 deaths would have been due to sporadic CJD. Two-thirds of cases of sporadic CJD worldwide are of the 129MM genotype and therefore it is not surprising that most cases of iatrogenic CJD outside the UK were of this genotype. However, in the present series, the pattern was different with the early patients, which were predominantly of the VV genotype. As only ∼24% of cases of sporadic CJD are 129VV the question arises as to why the UK patients differ from the rest of the world in this regard.

 

One possibility is that the screening of donors was more successful than suggested above and by chance only one or two cases of sporadic CJD were the source of the growth hormone and these had an atypical phenotype that occured more frequently in VV or MV cases. Alternatively many donors were included, however, a single VV or MV case had a particularly high titre of infective material in the pituitary. The profound influence of codon 129 in controlling human prion transmission barriers has been extensively modelled in transgenic mice expressing human PrP on a mouse PrP null background (Wadsworth et al., 2010). These studies have shown that transmission barriers to infection with classical CJD prions are asymmetric, dependent upon the codon 129 genotype of the prion source and the recipient (Wadsworth et al., 2010). Whereas, transgenic mice expressing human PrP 129 valine are highly susceptible to classical CJD prions regardless of the PrPSc type or codon 129 genotype of the inoculum (Collinge et al., 1995, 1996; Telling et al., 1995; Hill et al., 1997; Korth et al., 2003; Kobayashi et al., 2007; Wadsworth et al., 2008b), the absence of a transmission barrier to classical CJD prions is not uniformly observed in mice expressing human PrP 129 methionine in the absence of mouse PrP. Here, mismatch at residue 129 between the inoculum and host can significantly affect transmission. Thus while there appears to be no barrier to transmission of classical CJD prions from codon 129 methionine homozygous patients (Asante et al., 2002; Korth et al., 2003; Beringue et al., 2008; Kong et al., 2008), transmission of classical CJD prions from valine homozygous patients is often associated with more prolonged and variable incubation periods and reduced attack rates (Asante et al., 2002; Korth et al., 2003; Kobayashi et al., 2007, 2015). In the case of classical CJD prions from codon 129 heterozygous patients the transmission efficiency in transgenic mice expressing human PrP 129 methionine varies dependent upon PrPSc type and whether prions are propagated on human PrP with methionine or valine at residue 129 (Asante et al., 2002; Korth et al., 2003; Bishop et al., 2010; Kobayashi et al., 2015). These data provide an experimental background with which to interpret the temporal distribution of codon 129 genotypes within the cohort of iatrogenic CJD patients in the UK and suggest that the infecting prion contamination of growth hormone was from a VV or MV individual.

 

Finally, the significance of the polymorphism in RRP9 found on exome sequencing is unclear. The sample is small and the finding requires replication in an independent cohort. Any association could be related to either the initial condition for which the patients were treated or iatrogenic disease or both.

 

Mismatch of incubation period and rapidity of symptomatic progression A further seemingly paradoxical observation is that those recent clinical cases with particularly long incubation times have had the shortest clinical durations once symptomatic. Rates of clinical decline in our series of iatrogenic CJD have been most in keeping with observations of sporadic CJD with the MM genotype being more rapid than MV (Pocchiari et al., 2004). A plausible explanation for these observations is that the generation of a host prion strain compatible with host genotype occurs in the periphery during the prolonged incubation time; however, following CNS invasion the rapidity of disease progression [which is thought to be determined by the rates of production of toxic PrP species (designated PrPL for lethal); Hill et al., 2000; Collinge and Clarke, 2007; Sandberg et al., 2011, 2014] is more rapid in MM versus MV individuals owing to higher levels of homotypic substrate PrP available for conversion.

 

Conclusion

 

This study is the first to clearly define the clinical, imaging and neuro-pathological characteristics of patients with iatrogenic CJD due to cadaver-sourced growth hormone. It demonstrates that cases continue to occur at a low but steady rate in the UK and that the incubation period can be up to four decades. We have shown that all three common genotypes at PRNP are susceptible albeit with markedly different incubation periods, a phenomenon also seen in kuru. Whether similar susceptibility, with differing mean incubation times, will be seen in the UK related to the transmission of bovine spongiform encephalopathy prions remains to be seen. Further, we have demonstrated a dissociation between the incubation period and the rapidity of decline once a person develops symptoms.

 

Funding This work was funded by the UK Medical Research Council. The Cohort study was initially funded by the Department of Health (England) and has been funded since 2012 by the National Institute of Health Research’s Biomedical Research Centre at University College London Hospitals NHS Foundation Trust.

 

Conflict of interest J.C. is a Director and J.C. and J.D.F.W. are shareholders of D-Gen Limited which owns one of the antibodies used in this study.

 

Supplementary material Supplementary material is available at Brain online.

 

Acknowledgements We thank the National Prion Disease Monitoring Cohort steering committee- C Kennard, P Mills, V Farewell, P Chinnery, A Mackay, E Riboli, R Knight. We thank all the patients, their carers and families, who took part in the Cohort study and UK neurologists and the National CJD Surveillance Unit for referring patients. We thank officials at the Department of Health, Medical Research Council Research Management Group staff, co-chairs of the PRION-1 and Cohort trial steering committee, and our colleagues at the National CJD Research Surveillance Unit for establishing the National CJD referral and data sharing arrangements, without which these studies would not have been possible. We particularly acknowledge the contribution of J. Ironside and M. Bishop for providing genotypes at PRNP codon 129 in six cases previously unpublished. We thank all past and present colleagues at the National Prion Clinic (formerly at St Mary’s Hospital, London and now at the National Hospital for Neurology and Neurosurgery, Queen Square, London) in particular Kizzy Alner, Sylvia Gamazo- Navarro, Durre Siddique, Suvankar Pal, Thomas Webb, Diego Kaski, Dillip Gallujipali, Kathryn Prout, Nora Heard, Clare Morris, Rita Wilkinson, Chris Rhymes, Suzanne Hampson, Claire Petersen, Chris Carswell, Joanna Field, Elisabeth Morgan, Imogen Eastwood, Liz Ford, Jane Owen, Veronica O’Donnell, Michele Gorham, Ekaterina Kassidi, and Colm Treacy and at the Medical Research Council Clinical Trials Unit, in particular Michael Ranopa, Geraldine Keogh, Moira Spyer, Debbie Johnson, Liz Brodnicki, and Patrick Kelleher.

 

iatrogenic Creutzfeldt-Jakob disease growth hormone prion disease RRP9PRNP

 


 


 

P.69: Distinct pathological phenotypes of Creutzfeldt-Jakob disease in recipients of prion-contaminated growth hormone

 

Ignazio Cali1,2, Cathleen Miller3, Tetsuyuky Kitamoto4, Joseph Parisi5, Michael Geschwind6, Pierluigi Gambetti1, and Lawrence Schonberger7 1National Prion Disease Pathology Surveillance Center (NPDPSC); Department of Pathology; Case Western Reserve University; School of Medicine; Cleveland, OH USA; 2Department of Clinical and Experimental Medicine; Second University of Naples; Naples, Italy; 3Kaiser Permanente Vancouver Medical Center; Vancouver, WA USA; 4Graduate School of Medicine; Tohoku University; Sendai, Japan; 5Departments of Laboratory Medicine & Pathology and Neurology; Mayo Clinic; Rochester, MN USA; 6Department of Neurology; Memory and Aging Center; University of California; San Francisco, CA USA; 7National Center for Emerging and Zoonotic Infectious Diseases; Centers for Disease Control and Prevention; Atlanta, GA USA

 

The peripheral administration of growth hormone (GH) from prion-contaminated cadaveric pituitary glands is believed to be causative of iatrogenic Creutzfeldt-Jakob disease (iCJD) in more than 225 subjects worldwide. The present study describes the neuropathology and molecular features of 3 of the 30 identified iCJD cases among the approximately 7,700 recipients of cadaveric pituitary hormone in the US National Hormone and Pituitary Program (NHPP). All three cases were methionine (M) homozygous at codon 129 of the prion protein (PrP) gene (GH-CJDMM) and all received NHPP hormone produced before 1977 when a new hormone purification protocol was introduced that reduced the risk of prion contamination. Neuropathological examination revealed divergent phenotypes. The first phenotype, observed in the most recent US NHPP GH-CJD case, was characterized by the presence of amyloid plaques and reminiscent of sCJDMV2-K and, to some extent, variant CJD (vCJD). The second phenotype showed no plaques and shared several, but not all, characteristics with the sCJDMM(MV)1 subtype. However, PKresistant PrPSc (resPrPSc) from GH-CJDMM co-migrated with resPrPSc type 1 (GHCJDMM1) of sCJDMM1, but not with type 2 of sCJDMV2-K. Histopathological phenotypes with or without plaques also have been described in 2 groups of Japanese dura mater (d) graft-associated CJD (dCJD) with the same 129MM genotype but apparently different gel mobility of resPrPSc type 1. ***Our study suggests that phenotypic diversity in these iatrogenic diseases reflects adaptation of different exogenous prion strains to the 129MM host and/or to different locations of the initial PrPC to PrPSc conversion.

 


 


 

J Neurol Neurosurg Psychiatry 2002;72:792-793 doi:10.1136/jnnp.72.6.792 Short report

 

Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone

 

E A Croes1, G Roks1,*, G H Jansen3, P C G Nijssen2, C M van Duijn1

 

+ Author Affiliations 1Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands 2Department of Neurology, St Elisabeth Hospital, PO Box 90151, 5000 LC Tilburg, Netherlands 3Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands

 

Correspondence to: Professor C M van Duijn, Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Centre Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands; vanduijn@epib.fgg.eur.nl Received 27 December 2001 Accepted 12 March 2002 Revised 1 March 2002

 

Abstract

 

A 47 year old man is described who developed pathology proven Creutzfeldt-Jakob disease (CJD) 38 years after receiving a low dose of human derived growth hormone (hGH) as part of a diagnostic procedure. The patient presented with a cerebellar syndrome, which is compatible with iatrogenic CJD. This is the longest incubation period described so far for iatrogenic CJD. Furthermore, this is the first report of CJD after diagnostic use of hGH. Since the patient was one of the first in the world to receive hGH, other cases of iatrogenic CJD can be expected in the coming years.

 

snip...

 

An incubation period as long as 38 years had never been reported for iatrogenic CJD. Huillard d'Aignaux et al7 studied the incubation period in 55 patients with hGH related CJD in a cohort of 1361 French hGH recipients. The median incubation period was between 9 and 10 years. Under the most pessimistic model, the upper limit of the 95% confidence interval varied between 17 and 20 years. Although the infecting dose cannot be quantified, it can be speculated that the long incubation period in our patient is partly explained by the administration of a limited amount of hGH. This hypothesis is supported by experimental models, in which higher infecting doses usually produce shorter incubation periods.6 Since our patient was one of the first in the world to receive hGH, this case indicates that still more patients with iatrogenic CJD can be expected in the coming years. Another implication of our study is that CJD can develop even after a low dose of hGH. This case once more testifies that worldwide close monitoring of any form of iatrogenic CJD is mandatory.

 


 

SHORT REPORT

 

Creutzfeldt-Jakob disease 38 years after diagnostic use of human growth hormone

 


 

the warning shots fired over the bow of the boat that were never heard ;

 

PITUITARY EXTRACT

 

This was used to help cows super ovulate. This tissue was considered to be of greatest risk of containing BSE and consequently transmitting the disease...

 


 

NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE

 

snip...

 

I was quite prepared to believe in unofficial pituitary hormones, also in the 1970's, whether as described by Dr. Little, or in other circumstances, for animal use.

 

snip...

 

The fact that there were jars of pituitaries (or extract) around on shelves is attested by the still potent 1943 pituitaries, described in Stockell Hartree et al. (J/RF/17/291) which had come from the lab. at Mill Hill. Having taken the trouble to collect them, they were not lightly thrown out...

 


 

3. The extraction is from a pool of pituitary glands collected from abbatoirs and the process used is unlikely to have any effect on the BSE agent. Hormones extracted from human pituitary glands have been responsible for a small number of Creutzfeldt Jacob disease in man.

 


 

SEE LOOPHOLE ;

 


 

SEE LOOPHOLE SHOULD BE CLOSED ;

 


 


 

Superovulation and embryo recovery in Red deer (Cervus elaphus ) hinds.

 

Fennessy PF1, Fisher MW, Shackell GH, Mackintosh CG. Author information 1Invermay Agricultural Centre Private Bag Mosgiel New Zealand.

 

Abstract

 

In two experiments, Red deer hinds were synchronized with intravaginal progesterone and were given 4 d of treatment (3 d before progesterone withdrawal and 1 d after) with an ovine follicle stimulating hormone (FSH) preparation which had a claimed low level of luteinizing hormone (LH) contamination. In Experiment 1, 12 hinds received one of four FSH levels by osmotic minipump. Hinds were run with fertile stags, and laparotomy and embryo recovery were performed 9 d after progesterone withdrawal. The ovulation rates (mean of three hinds per dosage) were 1.0, 2.0, 4.3 and 15.3 (number of corpora lutea counted) for estimated daily dosages rates of 0.036, 0.071, 0.11 and 0.14 units FSH preparation/day; the response to the increasing dosage was exponential ...snip...end

 


 


 

ovine follicle stimulating hormone (FSH)

 

F8174 Sigma Follicle Stimulating Hormone from sheep pituitary Synonym: FSH

 


 

Sunday, August 02, 2015

 

*** TEXAS CWD, Have you been ThunderStruck, deer semen, straw bred bucks, super ovulation, and the potential TSE Prion connection, what if? ***

 


 


 

************

 

‘’I shall not forget the profound effect on my emotions when I visited these farms and was warmly welcomed because of the great benefits resulting from the application of louping-ill vaccine, wheras the chief purpose of my visit was to determine if scrapie was appearing in the inoculated sheep. The enquiry made the position clear. Scrapie was developing in the sheep vaccinated in 1935 and it was only in a few instances that the owner was associating the occurrence with louping-ill vaccination. The disease was affecting all breeds and it was confined to the animals vaccinated with batch 2.’’

 


 

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SOME OTHER HISTORY HERE PITUITARY HORMONES AND TSE PRION ;

 

In 1993 the Allar’s inquiry into the use of cadaver-derived pituitary hormones under The Australian Human Pituitary Hormone Program and the association with four medically acquired (iatrogenic) Creutzfeldt-Jakob disease (CJD) deaths recommended the formation of an Australian surveillance unit to monitor further cases of iatrogenic CJD in Australia.1 The Australian National Creutzfeldt-Jakob disease Registry (ANCJDR) was established in October 1993 at the Department of Pathology at the University of Melbourne. The monitoring of further Australian iatrogenic CJD cases related to pituitary hormone treatment for infertility or short stature and contaminated dura mater grafts remains one of the core objectives of the ANCJDR. However, the ANCJDR’s activities have changed to encompass the surveillance of all types of CJD including sporadic, genetic and variant CJD and other transmissible spongiform encephalopathies (TSEs) such as Gerstmann Sträussler-Sheinker Syndrome (GSS) and fatal familial insomnia (FFI).

 

see more here ;

 

Saturday, November 09, 2013

 

Surveillance for creutzfeldt-Jakob disease in Australia: update to December 2012

 


 

Background of Australian Human Pituitary Hormone Program From 1967 until 1985 2,100 Australians were treated with human pituitary hormones under the Australian Human Pituitary Hormone Program (AHPHP).

 

In similar programs in overseas countries the majority of recipients of human pituitary hormones (hPH) were treated with human growth hormone (hGH) for short statue. In Australia the Australian Human Pituitary Hormone Program (AHPHP) treated approximately 1570 woman and about 60 men for infertility using human pituitary gonadotrophin (hPG). Approximately 660 Australian children were treated for short statue with human growth hormone (hGH).

 

Five Australians may so far have developed and died from health-care associated (iatrogenic) Creutzfeldt-Jakob disease (CJD) after hPH treatment . The program was suspended in 1985 following CJD deaths of recipients of hGH in the United States and England.

 

All those treated with hPH are at low risk of developing CJD. There is no way of knowing if batches received by recipients were contaminated. To date there is no test to show if recipients are incubating CJD.

 

The AHPHP was run under the auspices of the Commonwealth Department of Health. The hormones were manufactured by the then government-owned Commonwealth Serum Laboratories in Melbourne.

 

The AHPHP was conceived and operated by the Human Pituitary Advisory Committee (HPAC) until its activities ceased in 1985 and the committee was disbanded.

 

From 1992 intense media and political pressure followed news of the first two deaths from iatrogenic CJD as the families demanded an explanation. The then Minister for Health, Senator Graham Richardson, ordered an independent inquiry.

 

Associate Professor Margaret Allars, an administrative law expert from the University of Sydney conducted the inquiry into the use of Pituitary Derived Hormones in Australia and Creutzfeldt-Jakob Disease, which reported in June 1994.

 

The inquiry report made a number of recommendations concerning the care of recipients, the establishment of support services and the formation of a ministerial advisory council.

 

Recipients of hPH now live with a health status of being at “low risk” of CJD. Current infection control guidelines refer to “low risk” patients. Recipients and their families also live with anxiety linked to the threat of contracting a disease which can lie dormant for decades and for which there is no test, treatment or cure.

 


 


 

Tuesday, November 23, 2010

 

Prosecutors call for prison terms for CJD growth hormone doctors

 


 

Tuesday, May 04, 2010

 

Review of the Human Pituitary Trust Account and CJD Issue 20 January 2010

 


 

Creutzfeldt-Jakob Disease, CJD Support Group for short statured children of the 1970's and 1980's. Recommendations for Unapproved/Unregistered recipients

 


 


 

wonder how Michael is doing today ??? hope is all well...

 

Mr. Michael O'Meara

 

Senator Bernardi Senator for South Australia Michael O’Meara 120 Port Road P.O. Box 250 Hindmarsh SA 5007 Kinglake 3763 24th February 24, 2009

 

Dear Senator Bernardi

 

Re; Senate Committee Inquiry on Men’s Health

 

It is with regret that the 60 page submission I was preparing for this inquiry was lost in the recent Kinglake Bushfire, along with all other property and possessions of mine, and I now submit an abbreviated submission. Under such personal adversity, I believe this submission falls within the Terms of Reference.

 

Its is with pleasure that this submission be accepted in accordance with your Notice Of Motion (276) published in November 2008, some 5 months after a Private Member Motion was read in the House of Representatives. The Member for McEwen (Ms Fran Bailey) read a very emotional speech in the House (Committee Room) on 16th June 2008, supported by the Member for Moore, (Dr Mal Washer) and further with bipartisan support by the Rudd Government - expressed by the Members of Page, (Ms Janelle Saffin) and Dobell, (Mr. Craig Thomson)

 

It is with my pleasure that I submit the following Submission on behalf of myself and all other (then) boys and men treated with Human Pituitary Hormones, unofficially, and not recorded, under the Australian Human Pituitary Hormone Program, and who have suffered, with both short term and long term side effects to the male endocrine system as a result of such Human Experimentation, and with such side effects that are irreversible.

 

Approved Recipients of Human Growth Hormone or Human Pituitary Gonadotrohpin were subjected to a Senate Inquiry in 1993, known as “The Allars Inquiry”, however – unapproved and/or “Off Program” recipients who were not included in the Allars Inquiry, and whom were not disclosed to the Department of Health and Aging, who are at the same risk of CJD, and were never advised of their risk, particularly unrecorded recipients of hPG at Prince Henry’s Hospital in Melbourne – hundreds of males. The Senate now records (1998) the “Allars Inquiry” was misled.

 

It is these Males who were “overtreated” with Human Pituitary Gonadotrophin1, who were “overstimulated” through invivo experimentation, with batches varying2 and causing dire consequences to physical, mental and reproductive health - those who were exposed to anabolic steroids (a carcinogenic) as a Growth Promotant with severe side effects. Particular Recommendations were presented and submitted to The Minister for Heath by Professor Margaret Allars in 1994, and further explored by the Senate Affairs Reference Committee in 1998. Of these numerous recommendations, I draw particular reference to Recommendation 5 m stating

 

That the settlement offer should not preclude a plaintiff making any future claim in relation to: (a) Other physical illnesses contracted by recipients which may be related to long term side effects of HPH treatment3 This submission is dedicated to the Infant boys, Toddlers boys, Prepubescent boys, Teenage boys, Young, Middle Aged and Elderly Men aged 2 to 101 – who were treated under such experimental Programs, exposed to Endocrine Disruptors during the 1970’s, particularly those whom were castrated and sterilized by the Australian Government and/or representatives engaged under the Health Act 1958. Such Section with the Act has since been repealed so that the “experimental nature” of “The Program” cannot happen again - following the “Allars Inquiry”. This does not repeal or repair the ongoing side effects. In particular, I dedicate this submission to the memory of the child who lost his life under these experimental programs at Prince Henry’s Hospital during the 1970’s4.

 

Please accept my gratitude with appreciation with your efforts in this forthcoming Inquiry.

 

Yours Faithfully

 

Michael O’Meara

 

PDF 159KB

 


 

see also ;

 

Michael was recruited into the growth hormone clinic at Prince Henry's Hospital in 1972 when he was just 10 years old. He was subjected to deep sleep therapy in April 1972. At this time he was administered the human growth hormone using products from cadavers. It has since been found that some of this material was contaminated, with a number of young recipients subsequently contracting and dying of the deadly Creutzfeldt-Jakob disease, or CJD.

 


 


 

SNIP...SEE MORE HERE ;

 

BSE INQUIRY DFAs

 


 

Sunday, May 18, 2008

 

BSE Inquiry DRAFT FACTUAL ACCOUNTS DFA's

 


 

Sunday, May 18, 2008

 

BSE, CJD, and Baby foods (the great debate 1999 to 2005)

 


 

Sunday, May 18, 2008

 

MAD COW DISEASE BSE CJD CHILDREN VACCINES

 


 


 


 


 

‘’I shall not forget the profound effect on my emotions when I visited these farms and was warmly welcomed because of the great benefits resulting from the application of louping-ill vaccine, wheras the chief purpose of my visit was to determine if scrapie was appearing in the inoculated sheep. The enquiry made the position clear. Scrapie was developing in the sheep vaccinated in 1935 and it was only in a few instances that the owner was associating the occurrence with louping-ill vaccination. The disease was affecting all breeds and it was confined to the animals vaccinated with batch 2.’’

 


 

Sunday, February 08, 2015

 

FDA SCIENCE BOARD TO THE FOOD AND DRUG ADMINISTRATION BOVINE HEPARIN BSE CJD TSE PRION Wednesday, June 4, 2014

 


 

KURU Transmissible Spongiform Encephalopthy TSE Prion Disease

 

*** Kuru Video ***

 

Kuru: The Science and The Sorcery

 


 

*** Scrapie Video

 


 

*** Human Mad Cow Video

 


 

*** USA sporadic CJD MAD COW DISEASE HAS HUGE PROBLEM Video

 


 

PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS

 

*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***

 

O18

 

Zoonotic Potential of CWD Prions

 

Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA

 

Chronic wasting disease (CWD) is a widespread and expanding prion disease in free-ranging and captive cervid species in North America. The zoonotic potential of CWD prions is a serious public health concern. Current literature generated with in vitro methods and in vivo animal models (transgenic mice, macaques and squirrel monkeys) reports conflicting results. The susceptibility of human CNS and peripheral organs to CWD prions remains largely unresolved. In our earlier bioassay experiments using several humanized transgenic mouse lines, we detected protease-resistant PrPSc in the spleen of two out of 140 mice that were intracerebrally inoculated with natural CWD isolates, but PrPSc was not detected in the brain of the same mice. Secondary passages with such PrPSc-positive CWD-inoculated humanized mouse spleen tissues led to efficient prion transmission with clear clinical and pathological signs in both humanized and cervidized transgenic mice. Furthermore, a recent bioassay with natural CWD isolates in a new humanized transgenic mouse line led to clinical prion infection in 2 out of 20 mice. These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.

 

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

 

***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***

 

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

 

P.105: RT-QuIC models trans-species prion transmission

 

Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA

 

The propensity for trans-species prion transmission is related to the structural characteristics of the enciphering and heterologous PrP, but the exact mechanism remains mostly mysterious. Studies of the effects of primary or tertiary prion protein structures on trans-species prion transmission have relied primarily upon animal bioassays, making the influence of prion protein structure vs. host co-factors (e.g. cellular constituents, trafficking, and innate immune interactions) difficult to dissect. As an alternative strategy, we used real-time quakinginduced conversion (RT-QuIC) to investigate trans-species prion conversion.

 

To assess trans-species conversion in the RT-QuIC system, we compared chronic wasting disease (CWD) and bovine spongiform encephalopathy (BSE) prions, as well as feline CWD (fCWD) and feline spongiform encephalopathy (FSE). Each prion was seeded into each host recombinant PrP (full-length rPrP of white-tailed deer, bovine or feline). We demonstrated that fCWD is a more efficient seed for feline rPrP than for white-tailed deer rPrP, which suggests adaptation to the new host.

 

Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD. ***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.

 

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

 

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***

 

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

 


 

HUMANS CWD ?

 

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 ;

 


 

Thursday, October 10, 2013

 

*************CJD REPORT 1994 increased risk for consumption of veal and venison and lamb**************

 


 

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.

 


 

Thursday, October 10, 2013

 

*** CJD REPORT 1994 increased risk for consumption of veal and venison and lamb

 


 

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.

 


 

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

 


 

now, let’s see what the authors said about this casual link, personal communications years ago. 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 ;

 


 

*** 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).

 


 

*** 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.

 


 

From: Terry S. Singeltary Sr.

 

Sent: Saturday, November 15, 2014 9:29 PM

 

To: Terry S. Singeltary Sr.

 

Subject: THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL 1984

 

THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE

 

R. G. WILL

 

1984

 

*** 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). (SEE LINK IN REPORT HERE...TSS) PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;

 

snip...

 


 

*** 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).***

 


 

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, Val erie 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 longe 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...TSS

 

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

 


 

2014

 

***Moreover, L-BSE has been transmitted more easily to transgenic mice overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.

 

***It has been suggested that some sporadic CJD subtypes in humans may result from an exposure to the L-BSE agent.

 

*** Lending support to this hypothesis, pathological and biochemical similarities have been observed between L-BSE and an sCJD subtype (MV genotype at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and another sCJD subtype (MM genotype) [15].

 

snip...

 

ttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213560/pdf/viruses-06-03766.pdf

 

Monday, October 10, 2011

 

EFSA Journal 2011 The European Response to BSE: A Success Story

 

snip...

 

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far

 

*** but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded.

 

*** Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

 

snip...

 


 


 

Thursday, August 12, 2010

 

Seven main threats for the future linked to prions

 

First threat

 

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

 

*** Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans.

 

*** These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

 

Second threat

 

snip...

 


 

Thursday, July 30, 2015

 

*** Professor Lacey believes sporadic CJD itself originates from a cattle infection number of cattle farmers falling victim to Creutzfeld-Jakob Disease is much too high to be mere chance ***

 


 

O35

 

J. Mikol1, S. Luccantoni-Freire1, E. Correia1, N. Lescoutra-Etchegaray1, V. Durand1, C. Dehen1, J.P. Deslys1, E. Comoy1

 

1Institute of Emerging Diseases and Innovative Therapies, Service of Prion Diseases, Atomic Energy Commission, 18 Route du Panorama 92265 Fontenayaux- Roses, France

 

E-mail: jacqueline.mikol@wanadoo.fr

 

Uncommon prion disease induced in macaque ten years after scrapie inoculation

 

Introduction: Bovine Spongiform Encephalopathy (BSE) is the single animal prion disease reputed to be zoonotic, inducing variant of Creutzfeldt-Jakob Disease (vCJD) in man, and therefore strongly conditioned the protective measures. Among different sources of animal prion diseases, we show here that after more than ten years of incubation, intracerebral injection of a sheep scrapie isolate can induce a prion disease in cynomolgus macaque, a relevant model of human situation towards several prion strains. Neuropathological studies showed classical and uncommon data.

 

Material and method: The cynomolgus macaque was intracerebrally exposed to a classical scrapie isolate issued from a naturally infected sheep flock. Upon onset of clinical signs, euthanasia was performed for ethical reasons. Classical methods of biochemistry and neuropathology were used.

 

Results: The three elements of the triad were present:

 

spongiosis was predominant in the cortex, the striatum, the cerebellum. Neuronal loss and gliosis were moderate.

 

The notable data were the following

 

(i) the brain was small, the atrophy involved mostly the temporal lobe in which axonal loss was histologically demonstrated

 

(ii) the spongiosis of the Purkinje cells was so intense that most of them were destroyed

 

(iii) there was a neuronal loss and a massive gliosis of the dorsomedialis nucleus of the thalamus

 

(iv) iron deposits were present in the lenticular nucleus. PrPres heavily distributed in the cortex, the basal ganglia and the cerebellum consisted in synaptic deposits and aggregates. Western Blot exhibited a type 1 PrPres in all parts of the brain.

 

Conclusion: We described here the successful transmission of a scrapie prion disease to a non-human primate after an extended incubation period, leading to a fatal, non-relapsing neurological disease with all the features of a prion disease. The cerebral lesional profile we observed was original in comparison to other animal prion diseases (c-BSE, L-type BSE, TME) we previously experimentally transmitted in this model.

 


 

Tuesday, December 16, 2014

 

Evidence for zoonotic potential of ovine scrapie prions

 

Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics

 

Abstract

 

Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human ​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE.

 

***The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans.

 

***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

 

Subject terms: Biological sciences• Medical research At a glance

 


 

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

 


 

1: J Infect Dis 1980 Aug;142(2):205-8

 

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

 

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

 

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

 

snip...

 

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

 

PMID: 6997404

 


 

Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasized by the finding that some strains of scrapie produce lesions identical to the once which characterize the human dementias"

 

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the scrapie problem urgent if the sheep industry is not to suffer grievously.

 

snip...

 

76/10.12/4.6

 


 

Nature. 1972 Mar 10;236(5341):73-4.

 

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).

 

Gibbs CJ Jr, Gajdusek DC.

 

Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

 

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

 

C. J. GIBBS jun. & D. C. GAJDUSEK

 

National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

 

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).

 


 


 


 


 

Friday, January 30, 2015

 

*** Scrapie: a particularly persistent pathogen ***

 


 

Thursday, March 26, 2015

 

Increased Infectivity of Anchorless Mouse Scrapie Prions in Transgenic Mice Overexpressing Human Prion Protein

 


 

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

 

J. Virol. doi:10.1128/JVI.01578-10 Copyright (c) 2010, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

 

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep.

 

Chris Plinston, Patricia Hart, Angela Chong, Nora Hunter, James Foster, Pedro Piccardo, Jean C. Manson, and Rona M Barron* Neuropathogenesis Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin, Midlothian, UK; Laboratory of Bacterial and TSE Agents, Food and Drug Administration, Rockville, MD, USA * To whom correspondence should be addressed. Email: rona.barron@roslin.ed.ac.uk .

 

Abstract

 

The risk of transmission of ruminant transmissible spongiform encephalopathy (TSE) to humans was thought to be low due to the lack of association between sheep scrapie and incidence of human TSE. However a single TSE agent strain has been shown to cause both bovine spongiform encephalopathy (BSE) and human vCJD, indicating that some ruminant TSEs may be transmissible to humans. While the transmission of cattle BSE to humans in transgenic mouse models has been inefficient, indicating the presence of a significant transmission barrier between cattle and humans, BSE has been transmitted to a number of other species. Here we aimed to further investigate the human transmission barrier following passage of BSE in a sheep. Following inoculation with cattle BSE, gene targeted transgenic mice expressing human PrP showed no clinical or pathological signs of TSE disease. However following inoculation with an isolate of BSE that had been passaged through a sheep, TSE associated vacuolation and proteinase-K resistant PrP deposition were observed in mice homozygous for the codon 129-methionine PRNP gene. This observation may be due to higher titres of the BSE agent in sheep, or an increased susceptibility of humans to BSE prions following passage through a sheep. ***However these data confirm that, contrary to previous predictions, it is possible that a sheep prion may be transmissible to humans and that BSE from other species may be a public health risk.

 


 


 

Suspect symptoms

 

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

 

28 Mar 01

 

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

 

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

 

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb...

 

2001

 

Suspect symptoms

 

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

 

28 Mar 01

 

Like lambs to the slaughter

 

31 March 2001

 

by Debora MacKenzie Magazine issue 2284.

 

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

 

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

 

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

 

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.

 

Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

 

Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.

 

As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.

 

"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.

 

But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

 

People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

 

But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."

 

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

 

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.

 


 

Like lambs to the slaughter

 

Thursday, December 20, 2012

 

OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED AND SAME OLD BSe WITH BOVINE MAD COW DISEASE

 


 

Monday, November 30, 2009

 

USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE

 


 

Monday, April 25, 2011

 

Experimental Oral Transmission of Atypical Scrapie to Sheep Volume 17, Number 5-May 2011

 


 

Friday, February 11, 2011

 

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

 


 

Monday, June 27, 2011

 

Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease

 


 

BSE: TIME TO TAKE H.B. PARRY SERIOUSLY

 

If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...

 


 

Thursday, January 15, 2015

 

41-year-old Navy Commander with sporadic Creutzfeldt–Jakob disease CJD TSE Prion: Case Report

 


 

Subject: *** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed with the extremely rare Creutzfeldt-Jakob disease aka mad cow type disease

 

what is CJD ? just ask USDA inc., and the OIE, they are still feeding the public and the media industry fed junk science that is 30 years old.

 

why doesn’t some of you try reading the facts, instead of rubber stamping everything the USDA inc says.

 

sporadic CJD has now been linked to BSE aka mad cow disease, Scrapie, and there is much concern now for CWD and risk factor for humans.

 

My sincere condolences to the family and friends of the House Speaker Becky Lockhart. I am deeply saddened hear this.

 

with that said, with great respect, I must ask each and every one of you Politicians that are so deeply saddened to hear of this needless death of the Honorable House Speaker Becky Lockhart, really, cry me a friggen river. I am seriously going to ask you all this...I have been diplomatic for about 17 years and it has got no where. people are still dying. so, are you all stupid or what??? how many more need to die ??? how much is global trade of beef and other meat products that are not tested for the TSE prion disease, how much and how many bodies is this market worth?

 

Saturday, January 17, 2015

 

*** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed with the extremely rare Creutzfeldt-Jakob disease

 


 

*** ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD strains, TSE prion aka Mad Cow Disease United States of America Update December 14, 2014 Report ***

 


 

*** Creutzfeldt-Jakob Disease Public Health Crisis VIDEO

 


 


 


 


 

Alzheimer’s, iatrogenic, what if ?

 


 

Friday, January 10, 2014

 

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

 


 

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

 

Tuesday, August 4, 2015

 

*** FDA U.S. Measures to Protect Against BSE ***

 


 

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

 

*** now, from all the consumption and exposure above, now think iatrogenic cjd tse prion at a hospital near you, what if?

 

TSS

 

Thursday, August 13, 2015

 

Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years

 

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