Is there evidence of vertical transmission of variant CJD ?

J Neurol Neurosurg Psychiatry doi:10.1136/jnnp.2009.172148

Is there evidence of vertical transmission of variant CJD?

Katy Murray (kmurray12@doctors.org.uk) + Author Affiliations

NationalCJD Surveillance Unit, United Kingdom James Peters (jimmypeters1980@yahoo.co.uk) + Author Affiliations

NationalCJD Surveillance Unit, United Kingdom Lesley Stellitano (lesley.stellitano@addenbrookes.nhs.uk) + Author Affiliations

Addenbrooke's Hospital, United Kingdom Annemarie Winstone (annemarie.winstone@addenbrookes.nhs.uk) + Author Affiliations

Addenbrooke's Hospital, United Kingdom Christopher Verity (christopher.verity@addenbrookes.nhs.uk) + Author Affiliations

Addenbrooke's Hospital, United Kingdom Robert Will (r.g.will@ed.ac.uk) + Author Affiliations

NationalCJD Surveillance Unit, United Kingdom Published Online First 27 April 2009 Abstract Objectives: The possibility of vertical transmission of variant CJD (vCJD) has been raised, because of the widespread distribution of infectivity in vCJD and the demonstration that this condition can be transmitted through blood transfusion. The aim is to search for evidence of this type of transmission of vCJD.

Methods: A national surveillance system for CJD has been established in the UK since 1990. Through this register details were extracted of all children born to vCJD cases up to March 2009. This list was checked against the CJD register and cases identified through the UK study of progressive intellectual and neurological deterioration in children (PIND) to determine whether any of the children of vCJD cases had themselves developed a progressive neurological disorder or vCJD.

Results: 125 children have been born to parents with a diagnosis of vCJD. Nine of these children were born to females with vCJD who were symptomatic at conception, birth or within a year of clinical onset. Only one woman was known to have breast fed her child. None of the children of vCJD cases have been referred to the NCJDSU as suspected vCJD and none have been classified as suffering from a progressive neurodegenerative disorder through the PIND study. One of the children has been investigated by the National Prion Unit (see accompanying case report).

Interpretation: To date there is no evidence of vertical transmission of vCJD. However, the incubation period through this mechanism might be prolonged and it will be many years before observational data can exclude this possibility.

http://jnnp.bmj.com/content/early/2009/04/27/jnnp.2009.172148.abstract




PLoS One. 2009; 4(9): e6929. Published online 2009 September 7. doi: 10.1371/journal.pone.0006929. PMCID: PMC2732902

Copyright Bencsik et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Possible Case of Maternal Transmission of Feline Spongiform Encephalopathy in a Captive Cheetah

Anna Bencsik,1* Sabine Debeer,1¤ Thierry Petit,2 and Thierry Baron1 1Unité ATNC, Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Lyon, France 2Zoo de La Palmyre, Les Mathes, France Neil Mabbott, Editor University of Edinburgh, United Kingdom * E-mail: a.bencsik@afssa.fr Conceived and designed the experiments: AAB. Performed the experiments: AAB SOD. Analyzed the data: AAB SOD TB. Contributed reagents/materials/analysis tools: AAB TP. Wrote the paper: AAB SOD TP TB. ¤Current address: INSERM Unité 851, Immunité Infection Vaccination, Tour CERVI, Lyon, France Received May 27, 2009; Accepted August 12, 2009.

Abstract

Feline spongiform encephalopathy (FSE) is considered to be related to bovine spongiform encephalopathy (BSE) and has been reported in domestic cats as well as in captive wild cats including cheetahs, first in the United Kingdom (UK) and then in other European countries. In France, several cases were described in cheetahs either imported from UK or born in France. Here we report details of two other FSE cases in captive cheetah including a 2nd case of FSE in a cheetah born in France, most likely due to maternal transmission. Complete prion protein immunohistochemical study on both brains and peripheral organs showed the close likeness between the two cases. In addition, transmission studies to the TgOvPrP4 mouse line were also performed, for comparison with the transmission of cattle BSE. The TgOvPrP4 mouse brains infected with cattle BSE and cheetah FSE revealed similar vacuolar lesion profiles, PrPd brain mapping with occurrence of typical florid plaques. Collectively, these data indicate that they harbor the same strain of agent as the cattle BSE agent. This new observation may have some impact on our knowledge of vertical transmission of BSE agent-linked TSEs such as in housecat FSE, or vCJD.



SNIP...


DISCUSSION


Here are reports of two cases of feline spongiform encephalopathy (FSE) in 2 female cheetahs, one imported from Great Britain, the other born in France, that most likely constitute the first description of a possible maternal transmission of this disease in that species. FSE is a transmissible spongiform encephalopathy (TSE) of the felidae, identified for several years now, in domestic and in captive wild felids, for the most part in cheetahs [21], [22]. In captivity, all these felidae could have been exposed to infected tissues from cattle from early in their lives and the most probable explanation of the occurrence of FSE is consequently a contamination by oral route with the infectious agent of the bovine spongiform encephalopathy (BSE). For FSE cases in domestic cats only, a link between BSE and FSE agent was demonstrated by the similarity of mean incubation periods and lesion profiles in FSE and BSE cases transmitted to wild-type mice [3], [23]. Here we report the transmission of the FSE case 1 (the mother of case 2) into the Tg(OvPrP4) mouse model that has been demonstrated as sensitive to and efficient at detecting the BSE strain of agent [2], [15], [16]. When BSE agent is transmitted in this model, at first passage the mean incubation periods may vary depending on the species of the host harboring the BSE agent (cattle, sheep etc.), and was reported to be from 300 d.p.i. +/-50 (mean +/- standard error) to 475 +/-69 d.p.i. (and even up to 500 d.p.i. +/-110 for an experimental ovine BSE in an ARR/ARR genotype sheep) [2], [15], [17].

For both passages reported in the present study, the mean incubation periods of FSE are totally in accordance with this previously reported range of data obtained in BSE agent transmission studies in TgOvPrP4 mice. It is likely that the slight differences between the incubation periods reported here in BSE and FSE transmissions resulted from the different species and different titre of infectious agent present in the inoculum. This was also suggested in other BSE transmission studies in RIII or C57Bl mouse lines, for which quite a wide range of mean incubation times has also been reported (range 393–909 days in BSE transmissions to C57Bl mice) [24]. At second passage, the incubation period for FSE appeared slightly longer, but this was not statistically different from the mean incubation period of the first passage experiment. The reason for this tendency is unclear but it had already been reported for ovine BSE transmitted to this model (296 d.p.i at first passage to 365 d.p.i at 2nd passage) [17]. However, it remained within the range of expected duration for BSE agent transmitted to this transgenic mouse model.

The comparison of FSE and BSE lesion profiles indicates clear resemblance in the shape and severity of vacuolation of the nine referential gray matter sites, consistent with the hypothesis of similarity between the infectious agents responsible for these TSE cases. In the same way, the systematic assessment of PrPd-accumulation sites and type revealed additional supportive arguments: PrPd depositions were also found in the cortex, septum, hippocampus, thalamus, hypothalamus, midbrain and brain stem, in structures all previously identified as accumulation sites in past experiments using different BSE sources [2], [15]–[17]. More characteristically in this transgenic mouse model, the typical amyloid florid plaques detected in each group indicated that the infectious agent present in the case of the mother cheetah was similar to the one responsible for the BSE in cattle. Collectively, these transmission data therefore clearly signified that the FSE case 1 was linked to the classical BSE agent.

As established for other species such as mink affected with transmissible mink encephalopathy [25], oral contamination appeared as the most obvious cause in that case. It is likely that this case, born in 1989 in a UK zoo, like other previously-described FSE cases in cheetah (born before 1986 and fed with cattle carcasses) [10]), was exposed to a BSE risk mainly during the first year of her life, before being exported in 1993 to Peaugres Safari Park in France. Contamination with another TSE source such as scrapie appears less likely, since scrapie is not transmittable to domestic cats, at least via the intracerebral route [26].

The occurrence of the second case reported here is of great interest since for this female cheetah the meat source was exclusively from rabbits and hens freshly killed or beef (minced steak fit for human consumption), every effort being made to avoid any possible risk of oral contamination with the BSE agent. In April 1996, immediately after the identification of the first cases of vCJD in the UK and France, essential precautionary measures were implemented, with a ban on the introduction of specified risk materials (SRM), including bovine brain and spinal cord, into the human and animal food chain. In addition, cheetahs are threatened with extinction and the species is classified as Vulnerable on the IUCN Red List, with subspecies venaticus and hecki classified as Critically Endangered. They appear on Annex I of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Captive specimens are managed in the context of breeding and conservation programs (EEP in Europe) where participating zoos including La Palmyre and Peaugres work in cooperation.

Moreover, lack of genetic diversity and the difficulty of breeding them in captivity make these animals very precious in zoological collections and they receive special care from the staff, including their diet which is evaluated for nutritional and sanitary risks. In addition, this female cheetah was not in contact with any other identified FSE-affected cheetah, except her mother. It therefore seems most likely that this female cheetah was contaminated through the vertical transmission of a prion agent related to BSE. The mother started to express the first clinical symptoms of FSE about 2 months before giving birth, suggesting that during the gestation as well as the suckling periods the little cheetah could have been exposed to the infectious agent from the mother. At the very least, these critical periods were those when the mother accumulated a maximum of PrPd. It is not possible to determine the precise way (in utero, via placenta, at birth, after birth via colostrums/milk) by which the infectious agent may have contaminated the young female cheetah. Anatomically, in the cheetah as in other carnivores, there is an endothelio-chorial placenta, a type of placenta facilitating exchanges between the mother and the fetus, in particular thanks to the proximity of their vascular elements. This is not the case of ruminants, which have an epithelio-chorial placenta and for which the risk of this type of transmission is thus very low. The mother gave birth to 5 individuals and 2 little cheetahs died in the first days after birth. At present, the 2 brothers of the FSE case 2 are still alive and healthy, living in 2 other, different French zoos, suggesting that the dose of infectious agent must not have been very high. In that context, the hypothesis of transmission of the disease via colostrums or milk is also credible, first because cellular as well as pathological forms of PrP have been detected in ruminant mammary glands [27], [28], second because PrPc (the acknowledged protein substrate for PrPd conversion) exists in the milk of domestic ruminants [27] and third because the possibility of transmitting the disease through milk and colostrums has recently been shown in the sheep species [29], [30]. In that hypothesis, the fact that PrPd was detectable in the lymph nodes of this cheetah is also remarkable because the lymphoreticular system seems to play a substantial role in facilitating neuroinvasion in the event of low doses of infective agent as demonstrated in a scrapie infection model of hamsters [31]. The age for onset of the disease (between 6 and 7 years) as well as the clinical symptoms seem to be comparable for the two FSE cases, and the fact that the incubation period was not shortened in the daughter is in accordance with the hypothesis of a low dose infection.

The comparison of PrPd brain mapping and type of deposition does not reveal obvious differences either in the brain structures affected or in the intensity of PrPd accumulation. The thalamo-cortical PrPd labeling might explain the sensorial dysfunctions observed in both cases, and the strong PrPd accumulation seen in the cerebellum may be at least a contributor to the loss of equilibrium. Finally the transmission studies of this second FSE case to TgOvPrP4 should make it possible to establish whether or not the parameters of the BSE strain reported here for the mother are stable.

In summary, although oral contamination by the BSE agent could not be totally excluded, the elements reported in the present article indicate collectively that the 2nd case of cheetah FSE, concerning an animal born in France, is most likely due to maternal transmission from a cheetah harboring the same strain of agent as the cattle BSE agent. Beside the epidemiological significance of this finding (and this may have some impact on our knowledge of FSE cases in domestic cats in which the possibility of a maternal transmission should be taken into account) it may have some incidence on the question of vertical transmission of other TSEs, especially those linked to the BSE agent. In the case of BSE in sheep, it appears that maternal transmission can occur [32], [33]. In cattle, there is no evidence of vertical transmission of either natural or experimental BSE even though the risk has been analyzed [34], but the peripheral pathogenesis of the BSE agent is also much more restricted, compared to the case of sheep or humans. Prion protein immunostaining and infectivity have been reported in lymphoreticular tissues in vCJD cases, as in the present FSE cases. Despite this, vertical transmission had not been found until now in vCJD cases. This question is still a current issue and a recent article underlines the caveats and difficulties in excluding this possibility, principally due to the limited availability of data concerning children in vCJD cases and a relatively short period of observation [35]. In this context, our article should bring additional elements for consideration in the hypothesis of a vertical transmission of the human disease linked to the BSE agent.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732902/



Journal of Virology, July 2005, p. 8665-8668, Vol. 79, No. 13 0022-538X/05/$08.00+0 doi:10.1128/JVI.79.13.8665-8668.2005 Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Vertical Transmission of Bovine Spongiform Encephalopathy Prions Evaluated in a Transgenic Mouse Model

J. Castilla,1 A. Brun,1 F. Díaz-San Segundo,1 F. J. Salguero,1 A. Gutiérrez-Adán,2 B. Pintado,2 M. A. Ramírez,2 L. del Riego,1 and J. M. Torres1* Centro de Investigación en Sanidad Animal (CISA-INIA), Ctra. de Valdeolmos a El Casar, Valdeolmos, 28130 Madrid, Spain,1 Departamento de Reproducción Animal y Conservación de Recursos Zoogenéticos (INIA), Avda. Puerta de Hierro s/n, Madrid 28040, Spain2

Received 4 November 2004/ Accepted 3 March 2005

In this work we show evidence of mother-to-offspring transmission in a transgenic mouse line expressing bovine PrP (boTg) experimentally infected by intracerebral administration of bovine spongiform encephalopathy (BSE) prions. PrPres was detected in brains of newborns from infected mothers only when mating was allowed near to the clinical stage of disease, when brain PrPres deposition could be detected by Western blot analysis. Attempts to detect infectivity in milk after intracerebral inoculation in boTg mice were unsuccessful, suggesting the involvement of other tissues as carriers of prion dissemination. The results shown here prove the ability of BSE prions to spread centrifugally from the central nervous system to peripheral tissues and to offspring in a mouse model. Also, these results may complement previous epidemiological data supporting the occurrence of vertical BSE transmission in cattle.


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* Corresponding author. Mailing address: Centro de Investigación en Sanidad Animal INIA, Valdeolmos, 28130 Madrid, Spain. Phone: 34 91 620 23 00. Fax: 34 91 620 22 47. E-mail: jmtorres@inia.es .


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Journal of Virology, July 2005, p. 8665-8668, Vol. 79, No. 13 0022-538X/05/$08.00+0 doi:10.1128/JVI.79.13.8665-8668.2005 Copyright © 2005, American Society for Microbiology. All Rights Reserved.


http://jvi.asm.org/cgi/content/abstract/79/13/8665




THE POSSIBLE VERTICAL TRANSMISSION OF BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) REPORT OF THE WORKING GROUP SUBMITTED TO THE SCIENTIFIC STEERING COMMITTEE AT ITS MEETING OF 18-19 MARCH 1999

http://ec.europa.eu/food/fs/sc/ssc/out44_en.pdf



Public Health and European CJD Surveillance Professor Robert Will University of Edinburgh, UK


Continuing public health concerns

•Prevalence of human BSE infection

•?Surgical transmission of vCJD

•?Vertical transmission of vCJD

•?Novel forms of human BSE infection (MV/VV)

•Atypical BSE/scrapie

•Chronic wasting disease of deer (North America)

•Countries exposed to BSE with inadequate animal or human surveillance



http://ec.europa.eu/food/animal/diseases/strategy/docs/Public_health_E_CJD_Surveillance_en.pdf



NEUROLOGY 1998;50:684-688 © 1998 American Academy of Neurology

Creutzfeldt-Jakob disease in a husband and wife

P. Brown, MD, L. Cervenáková, MD, L. McShane, PhD, L. G. Goldfarb, MD, K. Bishop, BS, F. Bastian, MD, J. Kirkpatrick, MD, P. Piccardo, MD, B. Ghetti, MD and D. C. Gajdusek, MD From the Laboratory of CNS Studies (Drs. Brown, Cervenáková, Goldfarb, and Gajdusek), NINDS, and Biometric Research Branch (Dr. McShane), NCI, National Institutes of Health, Bethesda, MD; the Department of Obstetrics (K. Bishop), Gynecology and Reproductive Sciences, University of Texas Houston Health Science Center, Houston, TX; the Department of Pathology (Dr. Bastian), University of South Alabama Medical Center, Mobile, AL; the Department of Pathology (Dr. Kirkpatrick), The Methodist Hospital, Houston, TX; and the Department of Pathology (Drs. Piccardo and Ghetti), Indiana University School of Medicine, Indianapolis, IN.

Address correspondence and reprint requests to Dr. Paul Brown, Building 36, Room 5B21, National Institutes of Health, Bethesda, MD 20892.

A 53-year-old man died of sporadic Creutzfeldt-Jakob disease (CJD) after a 1.5-year clinical course. Four and a half years later, his then 55-year-old widow died from CJD after a 1-month illness. Both patients had typical clinical and neuropathologic features of the disease, and pathognomonic proteinase-resistant amyloid protein ("prion" protein, or PrP) was present in both brains. Neither patient had a family history of neurologic disease, and molecular genetic analysis of their PrP genes was normal. No medical, surgical, or dietary antecedent of CJD was identified; therefore, we are left with the unanswerable alternatives of human-to-human transmission or the chance occurrence of sporadic CJD in a husband and wife.

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Received May 5, 1997. Accepted in final form September 10, 1997.


http://www.neurology.org/cgi/content/abstract/50/3/684





Monday, October 19, 2009

Atypical BSE, BSE, and other human and animal TSE in North America Update October 19, 2009

http://bse-atypical.blogspot.com/2009/10/atypical-bse-bse-and-other-human-and.html



2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006

http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html




Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html



Saturday, December 05, 2009

Molecular Model of Prion Transmission to Humans

http://creutzfeldt-jakob-disease.blogspot.com/2009/12/molecular-model-of-prion-transmission.html



Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/characteristics-of-established-and.html



Friday, December 11, 2009 Sporadic Creutzfeldt-Jakob disease causing a 2-years slowly progressive isolated dementia

http://creutzfeldt-jakob-disease.blogspot.com/2009/12/sporadic-creutzfeldt-jakob-disease.html



Sunday, August 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html



Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009

http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html



Thursday, December 17, 2009

An Unusual Case of Variant CJD 18 December 2009

http://creutzfeldt-jakob-disease.blogspot.com/2009/12/unusual-case-of-variant-cjd-18-december.html




TSS

Variant Creutzfeldt–Jakob disease: the first confirmed case from Portugal shows early onset, long duration and unusual pathology

J Neurol Neurosurg Psychiatry 2010;81:112-114 doi:10.1136/jnnp.2009.164293

Short report

Variant Creutzfeldt–Jakob disease: the first confirmed case from Portugal shows early onset, long duration and unusual pathology

C Barbot1, L Castro2, C Oliveira3, S Carpenter2 + Author Affiliations

1Department of Neuropaediatrics, Hospital Maria Pia, Porto, Portugal 2Anatomical Pathology Service, Hospital S João, Porto, Portugal 3Neurochemistry Laboratory, Department of Neurology, Hospitals of the University of Coimbra, Coimbra, Portugal Correspondence to Dr S Carpenter, Anatomic Pathology Service, Hospital São João, Alamêda Professor Hernani Monteiro, 4202-451 Porto, Portugal; scarpenter@mail.telepac.pt Received 2 October 2008 Revised 14 February 2009 Accepted 20 February 2009

Abstract

We present clinical and autopsy findings in the first case of variant Creutzfeldt–Jakob disease diagnosed and confirmed in Portugal. Onset was at 11 years, the earliest onset reported, and the course (32 months) relatively long. Western blot showed protease resistant prion protein, mainly of type 4 (2B) isoform. The cerebral cortex revealed severe spongiform change with numerous amyloid plaques, which did not fit the definition of florid plaques. In the striatum, spongiform change was limited but the extracellular space was dilated. Other reports have found marked spongiform change in the striatum and little in the cortex. Massive neuronal loss, in excess of what has been described, was found in the thalamus and pontine grey. The cerebellum showed, as expected, severe loss of granule cells, moderate loss of Purkinje cells and marked immunopositivity for the prion protein. Differences between our findings and previous ones probably result from the patient’s long survival.



http://jnnp.bmj.com/content/81/1/112.abstract




Thursday, December 3, 2009


FINAL REPORT OF A MISSION CARRIED OUT IN PORTUGAL FROM 11 TO 20 MAY 2009 IN ORDER TO EVALUATE MEASURES CONCERNING BOVINE SPONGIFORM ENCEPHALOPATHY


http://docket-aphis-2006-0041.blogspot.com/2009/12/final-report-of-mission-carried-out-in.html



Thursday, December 17, 2009

An Unusual Case of Variant CJD 18 December 2009


http://creutzfeldt-jakob-disease.blogspot.com/2009/12/unusual-case-of-variant-cjd-18-december.html




Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009

http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html




TSS

An Unusual Case of Variant CJD 18 December 2009

An Unusual Case of Variant CJD 18 December 2009

A Case Report published in this week’s The Lancet, written by Professor John Collinge, MRC Prion Unit and National Prion Clinic, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, reports the particular genetic make-up of a 30-year old man who has died of variant Creutzfeldt–Jakob disease (vCJD). The case report suggests that there could be other people with the condition who at the moment have no symptoms.

vCJD is caused by infectious agents called prions, which are made primarily of protein. The prions which cause vCJD are the same as those that cause bovine spongiform encephalopathy (BSE, also known as mad cow disease) in cows. Prion diseases affect the structure of the brain or other neural tissue, and all are currently untreatable and eventually fatal. Disease-causing prions are thought to consist of abnormally folded proteins that spread by encouraging the normal healthy prion protein found on the surface of most cells in the body to change shape. Prion diseases share similar disease mechanisms with Alzheimer’s, Parkinson’s, and other neurodegenerative brain diseases.

The 30-year-old man was admitted to hospital in June, 2008, with a 13-month history of personality change, progressive unsteadiness, and intellectual decline. He complained of severe leg pain and poor memory. Two months later he developed visual hallucinations. His symptoms worsened over the next three months. An MRI scan and other tests led to a diagnosis of vCJD. The man died in January 2009.

The case is unusual because tests showed the man had a particular genotype at his human prion protein gene (PRNP 129 codon), which can code for the amino acids valine (V) or methionine (M). People can be VV (homozygous), MM (again homozygous), or MV (heterozygous). Since 1994, around 200 cases of vCJD have been identified worldwide, and all those tested have been MM homozygous. However, the man in this Case Report was heterozygous.

Other prion diseases such as kuru or CJD associated with the use of pituitary hormones tend to have longer incubation periods in people who are PRNP heterozygous than those who are MM homozygous. The authors have recently reported some heterozygous patients with kuru had been incubating the disease over 50 years. Thus the authors believe there could be other cases like this one in which people are infected with vCJD but experiencing a long incubation period.

The authors say:

“The majority of the UK population have potentially been exposed to BSE prions but the extent of clinically silent infection remains unclear. About a third of the UK population are PRNP codon 129 methionine homozygous. If individuals with other genotypes are similarly susceptible to developing prion disease after BSE prion exposure, but with longer incubation periods, further cases, which may or may not meet diagnostic criteria for vCJD, would be expected in these PRNP codon 129 genotypes.”

They conclude:

“However, prion disease susceptibility and incubation periods are also affected by other genetic loci, and the possibility remains that cases of vCJD to date may have unusual combinations of genotypes at these loci, yet to be fully characterised.”

Press contact: 020 7637 6011 press.office@headoffice.mrc.ac.uk


http://www.mrc.ac.uk/Newspublications/News/MRC006556



Case Report

Variant CJD in an individual heterozygous for PRNP codon 129

Diego Kaski, Simon Mead, Harpreet Hyare, Sarah Cooper, Ravi Jampana, James Overell, Richard Knight, John Collinge, Peter Rudge

A 30-year-old man was admitted to hospital in June, 2008, with a 13-month history of personality change, progressive unsteadiness, and intellectual decline. He complained of severe leg pain and poor memory. 2 months later he de-veloped visual hallucinations and falsely believed he had an abdominal tumour. Symptoms worsened over the next 3 months. In October, 2008, his score on the mini mental state examination was 26/30. Pursuit eye movements were saccadic. He had a pout reflex. There was mild ataxia in the arms. His legs were severely ataxic with brisk tendon reflexes and a left extensor plantar response. He needed two crutches to walk. Medical history included tonsillectomy and removal of a cervical lymph node 15 years previously but he had never had a blood trans-fusion or received implantation of other human tissues.

EEG showed slow wave activity. CSF protein, glucose, and cell count were normal but the 14-3-3 protein was positive. MRI of the brain was consistent with the pulvinar sign (figure A). Although not all neuroradiologists con-sulted considered the pulvinar sign positive, quantitative assessment showed symmetrical higher signal in the pul-vinar nuclei than the caudate nuclei (figure B). Extensive screens for genetic, metabolic, and autoimmune diseases, including those induced by neoplasia, were negative. PRNP analysis did not show any known disease-associated mutations; codon 129 was heterozygous. A clinical diag-nosis of variant Creutzfeldt-Jakob disease (vCJD) was made on the basis of a characteristic clinical onset and progres-sion, exclusion of other diagnoses, and MRI findings. Sporadic CJD was judged unlikely given the combination of young age, clinical features, MRI findings, and absence of pseudoperiodic complexes on EEG. His carers did not want further investigation. His condition deteriorated and he died in January, 2009. Autopsy was not done.

Human prion diseases have acquired, sporadic, and inherited aetiologies, show wide phenotypic heterogeneity, and are associated with propagation of infectious prions of many distinct strain types.1 Since 1994, about 200 cases of vCJD, causally related to exposure to bovine spongiform encephalopathy (BSE) prions, have been identified world-wide. vCJD is generally seen in young adults, has charac-teristic neuropathological features and tissue distribution of infectivity, and a distinctive type 4 (London classifica-tion) molecular strain type.1 A polymorphism at codon 129 (encoding methionine or valine) of the human prion protein gene (PRNP), constitutes a powerful susceptibility factor in all types of prion disease. In vCJD, every case genotyped to date has been methionine homozygous. In the other acquired prion diseases, cases have occurred in all genotypes but with different mean incubation periods,1 which can span decades;2 PRNP codon 129 heterozygotes generally have the longest incubation periods. There is a report of a recipient of a blood transfusion from a donor incubating vCJD who died of unrelated causes but showed signs of prion infection at autopsy and was PRNP codon 129 heterozygous.3 Animal studies have suggested that different clinicopathological phenotypes could occur in people with various PRNP codon 129 genotypes.4,5 The majority of the UK population have potentially been exposed to BSE prions but the extent of clinically silent infection remains unclear. About a third of the UK population are PRNP codon 129 methionine homozygous. If individuals with other genotypes are similarly susceptible to developing prion disease after BSE prion exposure, but with longer incubation periods, further cases, which may or may not meet diagnostic criteria for vCJD, would be expected in these PRNP codon 129 genotypes. However, prion disease susceptibility and incubation periods are also affected by other genetic loci, and the possibility remains that cases of vCJD to date may have unusual combinations of genotypes at these loci, yet to be fully characterised.

Figure: MRI (A) Increased signal intensity in the pulvinar nucleus bilaterally (arrow). (B) MR signal intensity in the pulvinar (Pu) is higher than in the head of the caudate nuclei (C), putamen (P), and right frontal white matter (FWM).

Contributors

All authors were involved in discussion about diagnosis, care of the patient, and preparation of the report. Written consent to publish was obtained.

Conflicts of interest

JC is a director and shareholder of D-Gen Ltd, an academic spin-out company in the field of prion disease diagnosis, decontamination, and therapy. The other authors declare that they have no conflicts of interest.

References

1 Collinge J. Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 2001; 24: 519–50.

2 Collinge J, Whitfield J, McKintosh E, et al. Kuru in the 21st century–an acquired human prion disease with very long incubation periods. Lancet 2006; 367: 2068–74.

3 Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004; 364: 527–29.

4 Asante E, Linehan J, Gowland I, et al. Dissociation of pathological and molecular phenotype of variant Creutzfeldt-Jakob disease in transgenic human prion protein 129 heterozygous mice. Proc Natl Acad Sci USA 2006; 103: 10759–64.

5 Wadsworth JD, Asante E, Desbruslais M, et al. Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science 2004; 306: 1793–96.


http://press.thelancet.com/vcjd.pdf



Tuesday, December 15, 2009

Intraspecies transmission of L-type-like bovine spongiform encephalopathy detected in Japan

NOTE


http://bse-atypical.blogspot.com/2009/12/intraspecies-transmission-of-l-type.html



Monday, October 19, 2009

Atypical BSE, BSE, and other human and animal TSE in North America Update October 19, 2009


http://bse-atypical.blogspot.com/2009/10/atypical-bse-bse-and-other-human-and.html




2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006


http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html




Monday, December 14, 2009 R.I.P. MOM hvCJD December 14, 1997

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html



Saturday, December 05, 2009

Molecular Model of Prion Transmission to Humans


http://creutzfeldt-jakob-disease.blogspot.com/2009/12/molecular-model-of-prion-transmission.html



Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/characteristics-of-established-and.html



Friday, December 11, 2009 Sporadic Creutzfeldt-Jakob disease causing a 2-years slowly progressive isolated dementia


http://creutzfeldt-jakob-disease.blogspot.com/2009/12/sporadic-creutzfeldt-jakob-disease.html



Sunday, August 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html



Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009


http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html



TSS

Sporadic Creutzfeldt-Jakob disease causing a 2-years slowly progressive isolated dementia

----- Original Message -----
From: Terry S. Singeltary Sr.
To: CJD-L@LISTS.AEGEE.ORG
Sent: Friday, December 11, 2009 9:06 PM
Subject: Sporadic Creutzfeldt-Jakob disease causing a 2-years slowly progressive isolated dementia



Sporadic Creutzfeldt-Jakob disease causing a 2-years slowly progressive isolated dementia

Journal Behavioural Neurology Publisher IOS Press ISSN 0953-4180 (Print) 1875-8584 (Online) Issue Volume 21, Number 3-4 / 2009 DOI 10.3233/BEN-2009-0238 Pages 175-179 Subject Group Neurosciences

Authors Álvaro Machado1, Manuel Ribeiro2, Margarida Rodrigues1, Carla Ferreira1, Inês Baldeiras3, M. Helena Ribeiro3, Isabel Santana4, Rui Almeida5, Lígia Castro6, Stirling Carpenter6 1Neurology Department, Hospital de São Marcos, Braga, Portugal 2Neuroradiology Department, Hospital de São Marcos, Braga, Portugal 3Neurochemistry Laboratory, Hospitais da Universidade de Coimbra, Coimbra, Portugal 4Neurology Department, Hospitais da Universidade de Coimbra, Coimbra, Portugal 5Neurosurgery Department, Hospital de São Marcos, Braga, Portugal 6Pathology Department, Hospital de São João, Porto, Portugal

Abstract

A 47-year-old woman was seen for progressive behavioural and cognitive disturbances slowly evolving over a 1-year period. Neuropsychological evaluation disclosed moderate to severe impairment of all cortical functions. Besides this no other clinical abnormality was found. MRI diffusion weighted imaging disclosed hyperintense cortical lesions in a ribbon-like fashion, with restricted diffusivity. EEG showed no periodic sharp waves and CSF examination was normal, including protein 14.3.3. She was heterozygote on codon 129. Her cognitive function continued to decline and she was readmitted for further investigation at the 24th month of disease. Again no ataxia or involuntary movements were observed. MRI disclosed widespread hyperintense lesions over the entire cortex and, for the first time, also caudato-putaminal hyperintensity in T2-weighted images. EEG again failed to show periodic activity. Stereotactic biopsy disclosed moderate spongiform changes, astrocytosis and perivacuolar staining with prion-directed antibodies. Western blot analysis revealed prion type 2 mobility pattern. We discuss the clinical significance of this case: as dementia was the sole finding, and this was slowly-evolving over a 2-year period, MRI findings were the key factor suggesting a prion disease in a woman that otherwise would probably be diagnosed with a primary degenerative dementia.

Keywords Creutzfeldt-Jacob disease, DWI, MV2, MRI, MRS, SPECT

http://iospress.metapress.com/content/948763u728010504/



Thursday, December 3, 2009

FINAL REPORT OF A MISSION CARRIED OUT IN PORTUGAL FROM 11 TO 20 MAY 2009 IN ORDER TO EVALUATE MEASURES CONCERNING BOVINE SPONGIFORM ENCEPHALOPATHY

http://docket-aphis-2006-0041.blogspot.com/2009/12/final-report-of-mission-carried-out-in.html



Eurosurveillance, Volume 10, Issue 25, 23 June 2005 Articles Direcção de Serviços de Informação e Análise, Direcção-Geral da Saúde1

--------------------------------------------------------------------------------

Citation style for this article: Direcção de Serviços de Informação e Análise, Direcção-Geral da Saúde. First probable case of vCJD reported in Portugal. Euro Surveill. 2005;10(25):pii=2732. Available online:

http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=2732



Date of submission:

--------------------------------------------------------------------------------

First probable case of vCJD reported in Portugal

Direcção de Serviços de Informação e Análise, Direcção-Geral da Saúde, Lisboa, Portugal

The Portuguese Direcção-Geral da Saúde (Directorate-Genearl for Health) was recently informed of the first probable case of variant Creutzfeldt-Jakob disease (vCJD) in Portugal, with laboratory evidence (tonsil biopsy) [1]. The patient is 12 year old boy currently living with his parents and receiving specialist medical care. The case meets the European and Allied Countries Collaborative Study Group of CJD’s (EUROCJD) definition of probable vCJD (http://www.eurocjd.ed.ac.uk/def.htm) and has been confirmed by the United Kingdom’s National CJD Surveillance Unit. The patient does not have a history of travel to the United Kingdom.

References: 1.Direcção-Geral da Saúde. Variante da Doença de Creutzfeldt-Jakob - Comunicado. Press release, 9 June 2005.


(http://www.dgsaude.pt/upload/membro.id/ficheiros/i007107.pdf)



http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=2732



Ministério da Saúde

Direcção-Geral da Saúde

Comunicado

A Direcção-Geral da Saúde foi recentemente notificada da existência de um

primeiro caso provável de variante da Doença de Creutzfeldt-Jakob (vDCJ), com

evidência laboratorial.

Como é do conhecimento público, casos desta doença têm sido diagnosticados em

diversos países da União Europeia.

Trata-se de um doente jovem do sexo masculino, residente no respectivo domicílio

com os pais, cuja identidade deve ser protegida por razões técnicas e éticas, tanto

mais que se trata de doença que não se transmite através de contactos pessoa a

pessoa, pelo que não constitui qualquer risco para os seus conviventes ou contactos.

O doente encontra-se com assistência médica especializada.

Não existem indícios de quaisquer outros casos desta doença nem de quadros

clínicos suspeitos de variante da Doença de Creutzfeldt-Jakob.

Atendendo ao desejo expresso pela família não serão prestadas declarações

adicionais.

Lisboa, 2005-06-09

O Alto-Comissário e Director-Geral da Saúde

Professor Doutor José Pereira Miguel

http://www.dgsaude.pt/upload/membro.id/ficheiros/i007107.pdf



New vCJD case in Portugal The Portuguese Ministry of Health has announced a second suspected case of vCJD. The report is in Portuguese, titled “Segundo caso provável de variante da Doença de Creutzfeldt-Jacob,” dated February, 2, 2007. Direcção-Geral da Saúde


http://www.dgs.pt/



Comunicado A Direcção-Geral da Saúde recebeu no dia 19 de Fevereiro de 2007 a notificação, com evidência laboratorial, de um segundo caso provável de variante da Doença de Creutzfeldt-Jacob (vDCJ) numa jovem portuguesa residente no Continente. Por imposição ética não são fornecidos pormenores sobre o caso ora notificado. Informa-se, todavia, que não existem riscos para a Saúde Pública, incluindo para os contactos próximos da doente, uma vez que a doença em causa não se transmite de pessoa a pessoa. Lisboa, 20 de Fevereiro de 2007

snip

COMUNICADO

Em Fevereiro de 2007 foi notificado um caso de possível variante de Creutzfeldt- Jakob numa jovem de 14 anos.

Hoje, dia 12 de Fevereiro de 2009, comunica-se a morte dessa jovem. Durante todo este período a jovem doente foi acompanhada por uma equipa composta por pessoal médico e de enfermagem do Serviço Nacional de Saúde e por técnicos da Segurança Social.

Comunica-se, também, que relativamente a este caso estão a ser observadas todas as normas nacionais e europeias previstas para estas situações.

Este é o segundo óbito registado em Portugal com diagnóstico da variante da doença de Creutzfeldt-Jakob, não havendo outros casos notificados até à presente data.

De forma a proteger a família enlutada, não serão divulgados mais pormenores relativos ao óbito de hoje.

Lisboa, 12 de Fevereiro de 2009 O Director-Geral da Saúde Francisco George

http://www.dgs.pt/



R.I.P. ...TSS


J Neurol Neurosurg Psychiatry 2008;79:180-182 doi:10.1136/jnnp.2007.128389

Short report

Variant Creutzfeldt–Jacob disease: the second case in Portugal and in the same geographical region

Á Machado1, H Soares2, H Antunes2, Z Magalhães3, C Ferreira1, I Baldeiras4, M H Ribeiro4, I Santana5, J Ramalheira6, L Castro7, S Carpenter7 + Author Affiliations

1Neurology Department, Hospital de São Marcos, Braga, Portugal 2Adolescent Unit, Paediatrics Department, Hospital de São Marcos, Braga, Portugal 3Neuroradiology Department, Hospital de São Marcos, Braga, Portugal 4Neurochemistry Laboratory, Hospitais da Universidade de Coimbra, Coimbra, Portugal 5Neurology Department, Hospitais da Universidade de Coimbra, Coimbra, Portugal 6Neurophysiology Department, Hospital Geral de Santo António, Porto, Portugal 7Pathology Department, Hospital de São João, Porto, Portugal Dr Álvaro Machado, Serriço de Neurologia, Hospital de Sâo Marcos, Largo Carlos Amarante, Apartado 2242, 4700-Braga, Portngal; alvmac@gmail.com Received 26 June 2007 Revised 14 August 2007 Accepted 17 August 2007 Published Online First 31 August 2007

Abstract

We present the second variant Creutzfeldt–Jacob patient in the same district of northwest Portugal as was previously reported. A 14-year-old previously healthy girl had unexplained pain in the left leg, as well as psychiatric disturbances. This was shortly followed by progressive cognitive impairment, ataxia and generalised choreoatethosis. Neuropsychological assessment revealed severe frontal and medial temporal dysfunction, the posterior cortices being spared. An electroencephalogram was normal. CSF 14.3.3 protein was slightly positive. Magnetic resonance imaging showed the “hockey stick sign” and hyperintensities in the periaquedutal grey matter and in the right parietal cortex, the last with restriction to water molecule movement. SPECT revealed perfusion defects in the left frontotemporal and right parietal regions. PRNP gene sequencing showed no mutations, the patient being homozygous to methionine in codon 129. Five months after onset, immunocytochemical and immunoblotting analysis confirmed deposition of prion protein and a PrP4t electrophoretic pattern. The patient never travelled outside Portugal or received blood transfusions. She had surgical herniorrhaphy in 1998 (when catgut was used) and 2003. This is the second case in Portugal in a 2-year period and 20 km apart from each other, with no known common exposure apart from ingestion of cow meat. We discuss these case peculiarities and underline its epidemiological significance.

http://jnnp.bmj.com/content/79/2/180.abstract



Brussels, 16 May 2001

BSE: Scientists publish risk assessments for Costa Rica, Kenya, Slovenia and Romania

The Scientific Steering Committee (SSC) advising the European Commission on BSE related issues has today published its opinion on the Geographical Risk of Bovine Spongiform Encephalopathy (GBR) in Costa Rica, Kenya, Slovenia and Romania. The evaluation of the geographical risk of presence of BSE focuses on the risk for animals to incubate the disease. The Committee concludes that is highly unlikely that cattle infected with the BSE agent are present in domestic herds of Costa Rica (GBR level I). They found that this is unlikely but not excluded in the herds of Kenya and Slovenia (GBR level II) and that it is likely that BSE is present in the cattle herds of Romania (GBR level III) although this is not yet confirmed. Slovenia is the first accession country that is classified as GBR level II. All other accession countries evaluated so far have been classified at level III of Geographical BSE Risk. Similarly, all EU Member States are classified at level III except for Sweden, Finland and Austria (level II) and United Kingdom and Portugal (level IV).

The full text of the opinions is available at:

http://ec.europa.eu/food/fs/sc/ssc/outcome_en.html



http://docket-aphis-2006-0041.blogspot.com/2009/06/bovine-spongiform-encephalopathy-bse.html



The numbers of tested and positive cattle in each category in each EU Member State are published and updated regularly. Although the number of cases in the EU was increasing in 2001 and 2002, since 2003 the number of cases in the EU altogether is decreasing (EC, 2003; 2004). A total of over 10 million cattle were tested in the EU in 2004. Of these, 686 cattle were positive. Spain and Portugal were the only countries in the EU 15 Member States with an increase of cases in 2003, and Germany in 2004.

ftp://ftp.fao.org/docrep/fao/010/a1000e/a1000e02.pdf



Portugal BSE CASES

2001-110

2002-86

2003-133

2004-92

2005-13*

* Portugal - Data as of 31 March 2005.

http://www.fas.usda.gov/gainfiles/200509/146130887.pdf



51 CASES IN 2005 TOTAL


http://www.usatradeonline.gov/agworld.nsf/505c55d16b88351a852567010058449b/91142d01964ffee885257297004ac400/$FILE/E47017.PDF



GBR IV: confirmed at a higher level United Kingdom, Portugal


http://www.oie.int/boutique/extrait/06heim937950.pdf



A retrospective study of Creutzfeldt-Jakob disease in North of Portugal 1993-2002: demographic, clinical and neuropathological features


http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2003000600012&lng=en&nrm=iso&tlng=en



Eurosurveillance, Volume 1, Issue 6, 01 June 1996

Creutzfeldt-Jakob disease: results of an inquiry in the fifteen Member States of the European Union

see Portugal ;

http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=158



VARIANT CREUTZFELDT-JAKOB DISEASE

CURRENT DATA (OCTOBER 2009)

http://www.cjd.ed.ac.uk/vcjdworld.htm



Saturday, December 05, 2009

Molecular Model of Prion Transmission to Humans


http://creutzfeldt-jakob-disease.blogspot.com/2009/12/molecular-model-of-prion-transmission.html



Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/characteristics-of-established-and.html




From: TSS () Subject: Sporadic creutzfeldt-jakob disease in two adolescents (see sCJD, the big lie) Date: May 28, 2007 at 7:58 am PST

J Neurol Neurosurg Psychiatry. Published Online First: 23 May 2007. doi:10.1136/jnnp.2006.104570 © 2007 by BMJ Publishing Group Ltd

Original articles

Sporadic creutzfeldt-jakob disease in two adolescents

K Murray 1, D L Ritchie 1, M Bruce 2, C A Young 3, M Doran 3, J W Ironside 4 and R G Will 4* 1 NationalCJD Surveillance Unit, United Kingdom 2 Neuropathogenesis Unit, United Kingdom 3 Walton Centre for Neurology and Neurosurgery, United Kingdom 4 National CJD Surveillance Unit, United Kingdom

* To whom correspondence should be addressed. E-mail: r.g.will@ed.ac.uk.

Accepted 15 April 2007

Abstract

Background: Sporadic Creutzfeldt-Jakob disease (CJD) is a condition predominantly affecting older age groups, with cases aged less than 45 years rare and an age at onset or death of less than 20 years exceptional.

Methods: Data from the systematic study of sporadic CJD in the UK are available from 1970 onwards. Clinical and pathological data are reviewed in order to identify atypical cases, including those at the extremes of the age range of sporadic CJD. Detailed analysis of atypical cases is undertaken and in selected cases laboratory transmission studies are carried out in order to provide information on the characteristics of the infectious agent.

Results: In the UK two cases of sporadic CJD in adolescents have been identified, dying aged 16 and 20 years. The first case predated the epidemic of bovine spongiform encephalopathy and the characteristics of the second case, including laboratory transmission studies, are consistent with a diagnosis of sporadic rather than variant CJD.

Conclusion: The cases in this report indicate that sporadic CJD can develop at a very young age, that variant CJD is not the only form of CJD occurring in this age group and that neuropathological examination is essential to accurate diagnosis of human prion disease.


http://jnnp.bmj.com/cgi/content/abstract/jnnp.2006.104570v1



Sent: Monday May 28, 2007

Subject: THE BIG LIE SPORADIC CJD AND MAD COW DISEASEs i.e. TSE


Thursday, July 10, 2008


A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008



http://cjdmadcowbaseoct2007.blogspot.com/2008/07/novel-human-disease-with-abnormal-prion.html




Terry S. Singeltary Sr.

Molecular Model of Prion Transmission to Humans

Molecular Model of Prion Transmission to Humans

Michael Jones, Darren Wight, Rona Barron, Martin Jeffrey, Jean Manson, Christopher Prowse, James W. Ironside, and Mark W. Head

To assess interspecies barriers to transmission of transmissible spongiform encephalopathies (TSEs), we investigated the ability of disease-associated prion proteins (PrPd) to initiate conversion of the human normal cellular form of prion protein of the 3 major PRNP polymorphic variants in vitro. Protein misfolding cyclic amplifi cation showed that conformation of PrPd partly determines host susceptibility.

snip...

Conclusions

Our results are best appreciated in terms of the molecular interaction between seed PrPd and substrate PrPC, specifi cally the species-specifi c amino acid sequence and PRNP polymorphic status of PrPC and PrPd and the PrPd conformers involved (Table). Regardless of the seed PrP amino acid sequence, the PrPd conformers associated with bovine BSE, ovine BSE, and human vCJD were amplifi ed in the humanized mouse substrate and displayed similar PRNP-129 genotype preferences (PRNP-129MM >PRNP- 129MV >PRNP-129VV). In contrast, the PrPd conformer associated with the ovine scrapie strain, although sharing the same PrP amino acid sequence as the PrPd in ovine BSE, could not be amplifi ed in any of the PRNP humanized mouse substrates but could be amplifi ed in a sheep brain substrate. These observations are consistent with conformation of a TSE agent’s PrPd (rather than solely its amino acid sequence) having a role in determining the susceptibility of a host’s PrPC to conversion. They similarly suggest that these molecular factors could in turn have a powerful infl uence on disease susceptibility and incubation time.

To date, all clinical cases of vCJD have occurred in persons with the PRNP-129MM genotype, as might be predicted from the effi ciency of amplifi cation of BSE-related PrPd shown here. Extrapolating from these results, one would predict that the next genotypic group most likely to show susceptibility to the BSE agent would be heterozygous (MV) at codon 129 of the PRNP gene, as previously suggested from the corresponding in vivo transmission studies (14).

In the wake of BSE epidemics in the United Kingdom and elsewhere, enhanced surveillance has identifi ed apparently new TSEs (15), raising concerns regarding animal and human health. PMCA with suitable substrate sources could provide a rapid way to estimate the molecular component of transmission barriers for particular TSE agents between species, including humans. These estimates could thus indicate whether, like classical scrapie, the agents rep- resent little risk for human health or whether, like classical BSE, they represent cause for concern.

http://www.cdc.gov/eid/content/15/12/pdfs/2013.pdf



EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE

This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........


http://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf



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

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract



12/10/76

AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE

Office Note CHAIRMAN: PROFESSOR PETER WILDY

snip...

A The Present Position with respect to Scrapie A] The Problem

Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.

The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.

It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.

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 emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise 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 acrapie problem urgent if the sheep industry is not to suffer grievously.

snip...

76/10.12/4.6


http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf



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).


http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html



Epidemiology of Scrapie in the United States 1977


http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf



http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf




Tuesday, April 28, 2009

Nor98-like Scrapie in the United States of America


http://nor-98.blogspot.com/2009/04/nor98-like-scrapie-in-united-states-of.html




Scrapie USA


http://scrapie-usa.blogspot.com/



Monday, November 30, 2009

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


http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html




JOURNAL OF NEUROLOGY

MARCH 26, 2003

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States

Email Terry S. Singeltary:

flounder@wt.net

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?



http://www.neurology.org/cgi/eletters/60/2/176#535




Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009

August 10, 2009

Greetings,

I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. North America seems to have the most species with documented Transmissible Spongiform Encephalopathy's, most all of which have been rendered and fed back to food producing animals and to humans for years. If you look at the statistics, sporadic CJD seems to be rising in the USA, and has been, with atypical cases of the sCJD. I find deeply disturbing in the year of 2009, that Human Transmissible Spongiform Encephalopathy of any strain and or phenotype, of all age groups, and I stress all age groups, because human TSE's do not know age, and they do not know borders. someone 56 years old, that has a human TSE, that has surgery, can pass this TSE agent on i.e. friendly fire, and or passing it forward, and there have been documented nvCJD in a 74 year old. Remembering also that only sporadic CJD has been documented to transmit via iatrogenic routes, until recently with the 4 cases of blood related transmission, of which the origin is thought to be nvCJD donors. However most Iatrogenic CJD cases are nothing more than sporadic CJD, until the source is proven, then it becomes Iatrogenic. An oxymoron of sorts, because all sporadic CJD is, are multiple forms, or strains, or phenotypes of Creutzfeldt Jakob Disease, that the route and source and species have not been confirmed and or documented. When will the myth of the UKBSEnvCJD only theory be put to bed for good. This theory in my opinion, and the following there from, as the GOLD STANDARD, has done nothing more than help spread this agent around the globe. Politics and money have caused the terrible consequences to date, and the fact that TSEs are a slow incubating death, but a death that is 100% certain for those that are exposed and live long enough to go clinical. once clinical, there is no recourse, to date. But, while sub-clinical, how many can one exposed human infect? Can humans exposed to CWD and scrapie strains pass it forward as some form of sporadic CJD in the surgical and medical arenas? why must we wait decades and decades to prove this point, only to expose millions needlessly, only for the sake of the industries involved? would it not have been prudent from the beginning to just include all TSE's, and rule them out from there with transmission studies and change policies there from, as opposed to doing just the opposite? The science of TSE's have been nothing more than a political circus since the beginning, and for anyone to still believe in this one strain, one group of bovines, in one geographical location, with only one age group of human TSE i.e. nvCJD myth, for anyone to believe this today only enhances to spreading of these human and animal TSE's. This is exactly why we have been in this quagmire.

The ones that believe that there is a spontaneous CJD in 85%+ of all cases of human TSE, and the ones that do not believe that cattle can have this same phenomenon, are two of the same, the industry, and so goes the political science aspect of this tobacco and or asbestos scenario i.e. follow the money. I could go into all angles of this man made nightmare, the real facts and science, for instance, the continuing rendering technology and slow cooking with low temps that brewed this stew up, and the fact that THE USA HAD THIS TECHNOLOGY FIRST AND SHIPPED IT TO THE U.K. SOME 5 YEARS BEFORE THE U.S. STARTED USING THE SAME TECHNOLOGY, to save on fuel cost. This is what supposedly amplified the TSE agent via sheep scrapie, and spread via feed in the U.K. bovine, and other countries exporting the tainted product. BUT most everyone ignores this fact, and the fact that the U.S. has been recycling more TSE, from more species with TSEs, than any other country documented, but yet, it's all spontaneous, and the rise in sporadic CJD in the U.S. is a happenstance of bad luck ??? I respectfully disagree. To top that all off, the infamous BSE-FIREWALL that the USDA always brags about was nothing more than ink on paper, and I can prove this. YOU can ignore it, but this is FACT (see source, as late as 2007, in one recall alone, some 10,000,000 MILLION POUNDS OF BANNED MAD COW FEED WENT OUT INTO COMMERCE TO BE FED OUT, and most was never recovered. This was banned blood laced, meat and bone meal. 2006 was a banner year for banned mad cow protein going into commerce in the U.S. (see source of FDA feed ban warning letter below). I stress that the August 4, 1997 USA mad cow feed ban and this infamous BSE firewall, was nothing more than ink on paper, it was never enforceable.

I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route. This would further have to be broken down to strain of species and then the route of transmission would further have to be broken down. Accumulation and Transmission are key to the threshold from sub- clinical to clinical disease, and key to all this, is to stop the amplification and transmission of this agent, the spreading of, no matter what strain. In my opinion, to continue with this myth that the U.K. strain of BSE one strain TSE in cows, and the nv/v CJD one strain TSE humans, and the one geographical location source i.e. U.K., and that all the rest of human TSE are just one single strain i.e. sporadic CJD, a happenstance of bad luck that just happens due to a twisted protein that just twisted the wrong way, IN 85%+ OF ALL HUMAN TSEs, when to date there are 6 different phenotypes of sCJD, and growing per Gambetti et al, and that no other animal TSE transmits to humans ??? With all due respect to all Scientist that believe this, I beg to differ. To continue with this masquerade will only continue to spread, expose, and kill, who knows how many more in the years and decades to come. ONE was enough for me, My Mom, hvCJD i.e. Heidenhain Variant CJD, DOD 12/14/97 confirmed, which is nothing more than another mans name added to CJD, like CJD itself, Jakob and Creutzfeldt, or Gerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE, named after another human. WE are only kidding ourselves with the current diagnostic criteria for human and animal TSE, especially differentiating between the nvCJD vs the sporadic CJD strains and then the GSS strains and also the FFI fatal familial insomnia strains or the ones that mimics one or the other of those TSE? Tissue infectivity and strain typing of the many variants of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ...

please see history, and the ever evolving TSE science to date ;


Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009


http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html




Thursday, November 05, 2009

Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification


http://creutzfeldt-jakob-disease.blogspot.com/2009/11/incidence-and-spectrum-of-sporadic.html




Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

Brian S. Appleby, MD; Kristin K. Appleby, MD; Barbara J. Crain, MD, PhD; Chiadi U. Onyike, MD, MHS; Mitchell T. Wallin, MD, MPH; Peter V. Rabins, MD, MPH

Background: The classic Creutzfeldt-Jakob disease (CJD), Heidenhain, and Oppenheimer-Brownell variants are sporadic CJD (sCJD) phenotypes frequently described in the literature, but many cases present with neuropsychiatric symptoms, suggesting that there may be additional sCJD phenotypes.

Objective: To characterize clinical, diagnostic, and molecular features of 5 sCJD variants.

Design: Retrospective analysis.

Setting: The Johns Hopkins and Veterans Administration health care systems.

Participants: Eighty-eight patients with definite or probable sCJD.

Main Outcome Measures: Differences in age at onset, illness progression, diagnostic test results, and molecular subtype.

Results: The age at onset differed among sCJD variants (P=.03); the affective variant had the youngest mean age at onset (59.7 years). Survival time (P
.001) and the time to clinical presentation (P=.003) differed among groups. Patients with the classic CJD phenotype had the shortest median survival time from symptom onset (66 days) and those who met criteria for the affective sCJD variant had the longest (421 days) and presented to clinicians significantly later (median time from onset to presentation, 92 days; P=.004). Cerebrospinal fluid analyses were positive for 14-3-3 protein in all of the affective variants, regardless of illness duration. Periodic sharp-wave complexes were not detected on any of the electroencephalography tracings in the Oppenheimer-Brownell group; basal ganglia hyperintensity was not detected on brain magnetic resonance imaging in this group either. All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

Conclusions: The classic CJD phenotype and the Heidenhain, Oppenheimer-Brownell, cognitive, and affective sCJD variants differ by age at disease onset, survival time, and diagnostic test results. Characteristics of these 5 phenotypes are provided to facilitate further clinicopathologic investigation that may lead to more reliable and timely diagnoses of sCJD.

Arch Neurol. 2009;66(2):208-215

snip...

COMMENT

snip...see full text ;


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/characteristics-of-established-and.html






TSS

New guidance on decontamination of trial contact lenses and other contact devices has been revealed for CJD AND vCJD

New DoH guidance on decontaminating lenses

December 4th, 2009

New guidance on decontamination of trial contact lenses and other contact devices has been revealed.

The latest recommendations from the Department of Health’s Advisory Committee on Dangerous Pathogens (ACDP) replace previous guidance issued amid fears that Creutzfeldt-Jakob Disease (CJD) and variant CJD (vCJD), the human form of bovine spongiform encephalopathy (BSE, ‘mad cow disease’), could theoretically be transmitted from person to person by contact lenses and other devices such as tonometer heads and diagnostic lenses.

Details were discussed at the British Contact Lens Association’s Pioneers’ Conference in London late in November.

Professor Roger Buckley (pictured), a member of the ophthalmology subgroup of the ACDP’s Transmissible Spongiform Encephalopathy Working Group established to review this advice, told BCLA members at the Royal Society of Medicine that there had been no known cases of transmission of CJD/vCJD resulting from contact lens wear or diagnostic examination, and there was now thought to be a low level of risk of infectivity of the cornea and ocular surface.

Under the new guidance, six steps are required to minimise the risk of transmission via re-used contact devices. The lens or device should be: decontaminated immediately after contact with the eye surface; rinsed in Water for Irrigation BP (not tap water) for not less than 30 seconds; cleaned on all surfaces with a liquid soap or detergent, then rinsed in Water for Irrigation BP for a further 30 seconds; immersed in a freshly-prepared solution of sodium hypochlorite providing 10,000ppm of available chlorine for ten minutes; rinsed in three changes of Water for Irrigation BP for a total of not less than ten minutes; shaken to remove excess water, dried with a disposable tissue, and stored dry in a suitable container.

Any further measure (such as autoclaving) can then be carried out, if this is necessary and if the device is designed to withstand such a process. Otherwise, it is ready for immediate re-use.


http://www.optometry.co.uk/newsview.php?id=843




Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex C ANNEX C General principles of decontamination and waste disposal


http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_108602.pdf




Alert to Urological Surgeons TRANSRECTAL PROSTATIC BIOPSY IN MEN AT RISK OF VARIANT CJD


http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_106909.pdf





Ophthalmology

The Ophthalmology subgroup met twice in 2008 on 7th April and 20th June to discuss issues relating to CJD infection control in ophthalmology. The following topic groups were identified: 17 • Anterior eye • Posterior eye • Assessment tool • Decontamination of ophthalmic surgical instruments • Examination, diagnostic equipment and contact lenses • CJD incident management Members were assigned to relevant topic groups, and discussions and research were coordinated by a topic group lead. The topic groups then produced draft guidance on their particular areas of expertise towards the end of 2008. Pathology (Annex K) The Working Group drafted guidelines for pathologists and pathology laboratories for the handling of tissues from patients with, or at risk of, CJD. This document (Annex K of the Working Group guidance) is aimed at pathologists and individuals working in pathology laboratories who handle tissues from patients. It aims to ensure that laboratory staff are aware of risk factors for CJD prior to carrying out procedures on tissues. The draft annex was sent out for a limited consultation with representatives from the Royal College of Pathologists, the Institute for Biomedical Sciences, the British Neuropathological Society and the Health and Safety Executive. The Annex was approved by the Working Group at their December 2008 meeting. Annex K has since been published at:

http://www.advisorybodies.doh.gov.uk/acdp/tseguidance


Pre-surgery assessment (Annex J) The updates to Annex J were approved for publication by the Working Group at their February 2008 meeting, subject to some minor adjustments. The Annex was then signed off by the ACDP Chairman and published on 1st May 2008 at:


http://www.advisorybodies.doh.gov.uk/acdp/tseguidance



see full text ;


http://www.hse.gov.uk/aboutus/meetings/committees/acdp/ar2008.pdf




Friday, July 17, 2009

Revision to pre-surgical assessment of risk for vCJD in neurosurgery and eye surgery units Volume 3 No 28; 17 July 2009


http://creutzfeldt-jakob-disease.blogspot.com/2009/07/revision-to-pre-surgical-assessment-of.html



Six steps will minimise risk from trial lenses

Revised guidance on the decontamination of trial contact lenses and other contact devices has been released by the Department of Health's (DoH) Advisory Committee on Dangerous Pathogens (ACDP).

The new guidance replaces previous advice issued amid fears that Creutzfeldt-Jakob disease (CJD) and variant CJD, the human form of bovine spongiform encephalopathy (BSE), could theoretically be transmitted from person to person by contact lenses, tonometer heads and diagnostic lenses.

Under the new guidance, six steps are required to minimise the risk of transmission via re-used contact devices. The lens or device should be:

Decontaminated immediately after contact with the eye surface

Rinsed in Water for Irrigation BP (not tap water) for not less than 30 seconds

Cleaned on all surfaces with a liquid soap or detergent, then rinsed in Water for Irrigation BP for a further 30 seconds

Immersed in a freshly prepared solution of sodium hypochlorite providing 10,000ppm of available chlorine for 10 minutes

Rinsed in three changes of Water for Irrigation BP for a total of not less than 10 minutes

Shaken to remove excess water, dried with a disposable tissue, and stored dry in a suitable container.

Any further measure (such as autoclaving) can then be carried out, if this is necessary and if the device is designed to withstand such a process. Otherwise, it is ready for immediate re-use.

Speaking at the British Contact Lens Association's (BCLA) Pioneers' Conference in London on November 26, Professor Roger Buckley, a member of the ophthalmology subgroup of the ACDP's Transmissible Spongiform Encephalopathy Working Group set up to review the advice, said that there had been no known cases of transmission of CJD resulting from contact lens wear or diagnostic examination and there was now thought to be a low level of risk of infectivity of the cornea and ocular surface.

Professor Buckley told BCLA members that if the recommendations were not followed practitioners could be 'on their own medico-legally'.

The full guidance, entitled Managing CJD/vCJD risk in ophthalmology can be found on the DoH website.


http://www.opticianonline.net/Articles/2009/12/14/24605/Six+steps+will+minimise+risk+from+trial+lenses.html




Wednesday, August 20, 2008

Tonometer disinfection practice in the United Kingdom: A national survey



http://creutzfeldt-jakob-disease.blogspot.com/2008/08/tonometer-disinfection-practice-in.html



CJD Human Cornea Tissue, Recall END OF ENFORCEMENT REPORT FOR AUGUST 5, 2009
Posted Aug 07 2009 6:32pm


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjd-human-cornea-tissue-recall-end-of.html



http://stanford.wellsphere.com/cjd-article/cjd-human-cornea-tissue-recall-end-of-enforcement-report-for-august-5-2009/764280




From: TSS

Subject: Tonometer prism sterilisation: A local and UK national survey (TSE)

Date: August 24, 2007 at 1:24 pm PST

1: Cont Lens Anterior Eye. 2007 Aug 17; [Epub ahead of print]

Tonometer prism sterilisation: A local and UK national survey.

Chandra A, Barsam A, Hammond CJ. West Kent Eye Centre,
Princess Royal University Hospital, Orpington, Kent
BR6 8ND, UK.

PURPOSE: First to audit local adherence to a protocol of use of an alcohol
wipe for each tonometry, and secondly to assess current practice nationally
in the UK. METHOD: The audit was carried out at two units: The West Kent Eye
Centre at the Princess Royal University Hospital (Orpington, UK) and Queen
Mary's Hospital (Sidcup, UK). The standard set for this audit was 100%
sterilisation. During a 1-week period in November 2005, the number of
alcohol wipes was counted in each consultation room after outpatient
clinics, with the doctors being assessed blind to the survey. The number of
Goldman applanation tonometry intra-ocular pressures recorded by each
clinician was counted by inspection of the medical records of patients seen.
Secondly, departments listed in the UK Directory of Training Posts were
contacted by telephone and the senior nurse was interviewed. They were asked
directly about their department's tonometer prism sterilisation and
management. RESULTS: The local audit showed only 54% of tonometry
measurements were associated with sterilisation using an alcohol-impregnated
wipe. The national survey included 140 of the 152 UK training departments.
Thirty-three (23.6%) departments used disposable tonometer prisms routinely.
The remaining 107 (76.4%) used non-disposable prisms. Eighty-five (60.7%)
departments provided sodium hypochlorite for prism sterilisation, with 69
(81.2%) of these departments providing more than one prism/clinician to
allow full exposure to the disinfectant. Twenty-two (15.7%) departments used
alcohol wipes. Only 8 (7.5%) of the 107 departments using non-disposable
prisms tracked these prisms, despite Royal College of Ophthalmologists
guidelines that they should be. These same 8 (7.5%) departments replaced the
non-disposable prisms as per manufacturer guidelines. 19.3% of charge nurses
were aware of a policy for tonometry in patients with, or at risk of, prion
disease. CONCLUSIONS: This study highlights that sterilisation of tonometer
prisms was inconsistent in a local audit. Nationally, practices were varied.
The majority of ophthalmology departments continued to use non-disposable
tonometer prisms, but few seemed aware of the Royal College of
Ophthalmologists' recommendation that disposable prisms are used in patients
at risk of prion disease, and few track tonometer heads or replace them
according to manufacturers guidelines. Use of disposable tonometer prisms
would seem to reduce concerns about sterilisation, as well as prevent spread
of common pathogens.

PMID: 17703987 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov/sites/entrezDb=pubmed&Cmd=ShowDetailView&TermToSearch=17703987&ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum



143



PA-34

SPORADIC CREUTZFELDT-JAKOB DISEASE: PRPRES IS CONSTANTLY PRESENT IN THE RETINA, AND RARELY IN THE OPTIC NERVE

M. Mangieri1, G. Giaccone1, L. Limido1, G. Di Fede1, S. Suardi1, R. Capobianco1, P. Fociani2, O. Bugiani1, F. Tagliavini1 1 Istituto Nazionale Neurologico Carlo Besta, Division of Neuropathology and Neurology 5, Milano, Italy and 2 Ospedale Luigi Sacco, Division of Pathology, Università di Milano, Milano, Italy

e-mail: mmangieri@istituto-besta.it

Creutzfeldt-Jakob disease (CJD) is marked by the presence of the protease-resistant prion protein (PrPres) in the brain. Studies of the retina and optic nerve in patients with CJD are scanty and on very small series of patients. We analysed ocular tissues of sporadic CJD patients (retina of 58 and optic nerve of 51), representing all combinations of PRNP codon 129 polymorphisms and PrPres types by Parchi, except VV1. Ocular tissue from 24 patients with other neurological diseases were used as controls. The ocular tissue was collected at autopsy and the samples were fixed in Carnoy solution or frozen. Before immunohistochemistry with 3F4 antibody, the sections were pretreated with proteinase K and guanidine thiocyanate. In all cases of sCJD the retina showed immunoreactivity for PrPres localized in the inner and outer plexiform layers, with a synaptic type of labelling. No difference in the pattern of labeling was detected between CJD patients with different PRNP codon 129 polymorphisms and PrPres types in the brain. In all cases with frozen retinal tissue available (n = 18), the immunoblot was positive for PrPres . Two out of the 51 sCJD showed the deposition of PrPres also in the optic nerve, corresponding to an immunostaining delineating stellate cells and associated with the presence of numerous CD68- and CD45-positive cells. Our results demonstrate the presence of the pathological form of prion protein not only in the retina of all sCJD cases analysed, but also in optic nerve in a small subset of sCJD patients, a finding previously described only in variant CJD and in experimental animal models. Moreover, our data suggest a correlation between the deposition of PrPres and inflammatory changes in the optic nerve in sCJD.



http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf



----- Original Message -----
From: "Terry S. Singeltary Sr." <[log in to unmask]>
To: <[log in to unmask]>
Sent: Thursday, December 28, 2006 10:23 AM
Subject: Ophthalmic Surgery in Prion Diseases


Volume 13, Number 1–January 2007

Dispatch

Ophthalmic Surgery in Prion Diseases

Tsuyoshi Hamaguchi,*1 Moeko Noguchi-Shinohara,* Yosikazu Nakamura,†2 Takeshi
Sato,‡2 Tetsuyuki Kitamoto,§2 Hidehiro Mizusawa,¶2 and Masahito Yamada*2
*Kanazawa University Graduate School of Medical Science, Kanazawa, Japan;
†Jichi Medical University, Shimotsuke, Japan ‡National Center for Neurology
and Psychiatry, Ichikawa, Japan; §Tohoku University Graduate School of
Medicine, Sendai, Japan; and ¶Tokyo Medical and Dental University, Tokyo,
Japan

Suggested citation for this article

Abstract
Eleven (1.8%) of 597 patients underwent ophthalmic surgery within 1 month
before the onset of prion disease or after the onset. All ophthalmologists
reused surgical instruments that had been incompletely sterilized to
eliminate infectious prion protein. Ophthalmologists should be aware of
prion diseases as a possible cause of visual symptoms and use disposable
instruments whenever possible.

Visual impairment occurs in 10% to 20% of patients with sporadic
Creutzfeldt-Jakob disease (sCJD) during an early stage of the disease
(Heidenhain variant) (1,2). Some patients with prion diseases may visit
ophthalmologists with visual impairment due to prion diseases or with
coexisting age-related eye diseases (3,4).

Infectious prion protein (PrPSc) was identified in the retina and optic
nerve in patients with variant CJD (vCJD) and sCJD (5,6), and CJD has been
transmitted by corneal transplantation (7,8). In the World Health
Organization (WHO) guidelines, eyes were classified as highly infectious
tissues (9).

Secondary transmission of PrPSc through ophthalmic surgery could possibly be
prevented around the onset of prion diseases, although surgery that is
performed long before the onset of prion diseases would not have that
potential. It is important to understand the current status of ophthalmic
surgery for patients with prion diseases and to clarify the clinical
features of the patients with prion diseases who undergo ophthalmic surgery.
Here, we describe the relevant data from CJD surveillance in Japan.

The Study.....snip full text ;


http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0612&L=sanet-mg&P=24255


----- Original Message -----
From: "Terry S. Singeltary Sr." <[log in to unmask]>
To: <[log in to unmask]>
Sent: Wednesday, December 27, 2006 12:21 PM
Subject: ABNORMAL PRION ACCUMULATION ASSOCIATED WITH RETINAL PATHOLOGY IN
EXPERIMENTALLY INOCULATED SCRAPIE-AFFECTED SHEEP


http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0612&L=sanet-mg&P=24048


Eye procedure raises CJD concerns

November 19, 2004 United Press International by STEVE MITCHELL

A New York man who died from a rare brain disorder similar to mad cow disease in May underwent an eye procedure prior to his death that raises concerns about the possibility of transmitting the fatal disease to others, United Press International has learned.
The development comes on the heels of the announcement Thursday by U.S. Department of Agriculture officials of a possible second case of mad cow disease in U.S. herds.

Richard Da Silva, 58, of Orange County, N.Y., died from Creutzfeldt Jakob disease, an incurable brain-wasting illness that strikes about one person per million.

Richard's wife Ann Marie Da Silva told UPI he underwent a check for the eye disease glaucoma in 2003, approximately a year before his death. The procedure involves the use of a tonometer, which contacts the cornea -- an eye tissue that can contain prions, the infectious agent thought to cause CJD.

Ann Marie's concern is that others who had the tonometer used on them could have gotten infected.

A 2003 study by British researchers suggests her concerns may be justified. A team led by J.W. Ironside from the National Creutzfeldt-Jakob Disease Surveillance Unit at the University of Edinburgh examined tonometer heads and found they can retain cornea tissue that could infect other people -- even after cleaning and decontaminating the instrument.

"Retained corneal epithelial cells, following the standard decontamination routine of tonometer prisms, may represent potential prion infectivity," the researchers wrote in the British Journal of Ophthalmology last year. "Once the infectious agent is on the cornea, it could theoretically infect the brain."

Prions, misfolded proteins thought to be the cause of mad cow, CJD and similar diseases, are notoriously difficult to destroy and are capable of withstanding most sterilization procedures.

Laura Manuelidis, an expert on these diseases and section chief of surgery in the neuropathology department at Yale University, agreed with the British researchers that tonometers represent a potential risk of passing CJD to other people.

Manuelidis told UPI she has been voicing her concern about the risks of corneas since 1977 when her own study, published in the New England Journal of Medicine, showed the eye tissue, if infected, could transmit CJD.

At the time the procedure was done on Richard Da Silva, about a year before he died, she said it was "absolutely" possible he was infectious.

The CJD Incidents Panel, a body of experts set up by the U.K. Department of Health, noted in a 2001 report that procedures involving the cornea are considered medium risk for transmitting CJD. The first two patients who have a contaminated eye instrument used on them have the highest risk of contracting the disease, the panel said.

In 1999, the U.K. Department of Health banned opticians from reusing equipment that came in contact with patients' eyes out of concern it could result in the transmission of variant CJD, the form of the disease humans can contract from consuming infected beef products.

Richard Da Silva was associated with a cluster of five other cases of CJD in southern New York that raised concerns about vCJD.

None of the cases have been determined to stem from mad cow disease, but concerns about the cattle illness in the United States could increase in light of the USDA announcement Thursday that a cow tested positive on initial tests for the disease. If confirmed, this would be the second U.S. case of the illness; the first was detected in a Washington cow last December. The USDA said the suspect animal disclosed Thursday did not enter the food chain. The USDA did not release further details about the cow, but said results from further lab tests to confirm the initial tests were expected within seven days.

Ann Marie Da Silva said she informed the New York Health Department and later the eye doctor who performed the procedure about her husband's illness and her concerns about the risk of transmitting CJD via the tonometer.

The optometrist -- whom she declined to name because she did not want to jeopardize his career -- "didn't even know what this disease was," she said.

"He said the health department never called him and I called them (the health department) back and they didn't seem concerned about it," she added. "I just kept getting angrier and angrier when I felt I was being dismissed."

She said the state health department "seems to have an attitude of don't ask, don't tell" about CJD.

"There's a stigma attached to it," she said. "Is it because they're so afraid the public will panic? I don't know, but I don't think that the answer is to push things under the rug."

New York State Department of Health spokeswoman Claire Pospisil told UPI she would look into whether the agency was concerned about the possibility of transmitting CJD via tonometers, but she had not called back prior to story publication.

Disposable tonometers are readily available and could avoid the risk of transmitting the disease, Ironside and colleagues noted in their study. Ann Marie Da Silva said she asked the optometrist whether he used disposable tonometers and "he said 'No, it's a reusable one.'"

Ironside's team also noted other ophthalmic instruments come into contact with the cornea and could represent a source of infection as they are either difficult to decontaminate or cannot withstand the harsh procedures necessary to inactivate prions. These include corneal burrs, diagnostic and therapeutic contact lenses and other coated lenses.

Terry Singletary, whose mother died from a type of CJD called Heidenhain Variant, told UPI health officials were not doing enough to prevent people from being infected by contaminated medical equipment.

"They've got to start taking this disease seriously and they simply aren't doing it," said Singletary, who is a member of CJD Watch and CJD Voice -- advocacy groups for CJD patients and their families.

U.S. Centers for Disease Control and Prevention spokeswoman Christine Pearson did not return a phone call from UPI seeking comment. The agency's Web site states the eye is one of three tissues, along with the brain and spinal cord, that are considered to have "high infectivity."

The Web site said more than 250 people worldwide have contracted CJD through contaminated surgical instruments and tissue transplants. This includes as many as four who were infected by corneal grafts. The agency noted no such cases have been reported since 1976, when sterilization procedures were instituted in healthcare facilities.

Ironside and colleagues noted in their study, however, many disinfection procedures used on optical instruments, such as tonometers, fail. They wrote their finding of cornea tissue on tonometers indicates that "no current cleaning and disinfection strategy is fully effective."

Singletary said CDC's assertion that no CJD cases from infected equipment or tissues have been detected since 1976 is misleading.

"They have absolutely no idea" whether any cases have occurred in this manner, he said, because CJD cases often aren't investigated and the agency has not required physicians nationwide report all casesof CJD.

"There's no national surveillance unit for CJD in the United States; people are dying who aren't autopsied, the CDC has no way of knowing" whether people have been infected via infected equipment or tissues, he said.

Ann Marie Da Silva said she has contacted several members of her state's congressional delegation about her concerns, including Rep. Sue Kelly, R-N.Y., and Sen. Charles Schumer, D-N.Y.

"Basically, what I want is to be a positive force in this, but I also want more of a dialogue going on with the public and the health department," she said.



http://www.upi.com/NewsTrack/Science/2004/11/18/eye_procedure_raises_cjd_concerns/2974/




http://www.organicconsumers.org/madcow/CJD111904.cfm






Cadaver corneal transplants -- without family permission
Houston, Texas channel 11 news 28 Nov 99
Reported by Terry S. Singeltary Sr.son of CJD victim



http://www.mad-cow.org/dec99_news.html#bbb





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@uni-karlsruhe.de


######### Bovine Spongiform Encephalopathy #########

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...


http://www.mad-cow.org/~tom/dec99_news.html#bbb



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

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.

http://www.chron.com/cs/CDA/story.hts/metropolitan/669555

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

THE LEGALITY OF STEALING ORGAN/TISSUE...

TEXAS STATUTES

Sec. 693.012. Removal of Corneal Tissue Permitted Under Certain
Circumstances.

On a request from an authorized official of an eye bank for corneal
tissue, a justice of the peace or medical examiner may permit the
removal of corneal tissue if:

(1) the decedent from whom the tissue is to be removed died under
circumstances requiring an inquest by the justice of the peace or
medical examiner;

(2) no objection by a person listed in Section 693.013 is known by the
justice of the peace or medical examiner; and

(3) the removal of the corneal tissue will not interfere with the
subsequent course of an investigation or autopsy or alter the decedent's
postmortem facial appearance.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th
Congress. The 76th session of the Texas Legislature has concluded. The
State of Texas has not yet made the new codes available to the public.
Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.012

--------------------------------------------------------

TEXAS STATUTES

Sec. 693.003. Consent Required in Certain Circumstances.

(a) A medical examiner or a person acting on the authority of a medical
examiner may not remove a visceral organ unless the medical examiner
or person obtains the consent of a person listed in Section 693.004.

(b) If a person listed in Section 693.004 is known and available within
four hours after death is pronounced, a medical examiner or a person
acting on the authority of a medical examiner may not remove a
nonvisceral organ or tissue unless the medical examiner or person
obtains that person's consent.

(c) If a person listed in Section 693.004 cannot be identified and
contacted within four hours after death is pronounced and the medical
examiner determines that no reasonable likelihood exists that a person
can be identified and contacted during the four-hour period, the medical
examiner may permit the removal of a nonvisceral organ or tissue.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th
Congress. The 76th session of the Texas Legislature has concluded. The
State of Texas has not yet made the new codes available to the public.
Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.003

--------------------------------------------------------

PLEASE NOTE; the bottom would only pertain to those who know of the
law. if you don't know about it, you cannot dispute, so in four hours,
they can legally remove body organs, as long as they don't disfigure.
and who is to know the difference? makes me wonder of some of my dead
relatives, and if they were burried with their eye's and or any of their
organs. This is very disturbing, if not for moral reasons, but for the
risk of dangerous pathogens (human TSE's, etc.) to be transmitted. only
time will tell, but i am very disturbed.
these laws are not morally correct. They should be re-written as to they
cannot so easily take your organs, with no one knowing. The Family or
Victim, must consent. There should be some kind of research
on donor/family medical history...TSS

--------------------------------------------------------


Sec. 693.013. Persons Who May Object to Removal.

The following persons may object to the removal of corneal tissue:

(1) the decedent's spouse;

(2) the decedent's adult children, if there is no spouse;

(3) the decedent's parents, if there is no spouse or adult child; or

(4) the decedent's brothers or sisters, if there is no spouse, adult
child, or parent.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th
Congress. The 76th session of the Texas Legislature has concluded. The
State of Texas has not yet made the new codes available to the public.
Until they do, search the bill text for any changes or amendments.

Search 1999 Legislation for: 693.013

-------------------------------------------------------

to cover one's butt....

Sec. 693.014. Immunity From Damages in Civil Action.

(a) In a civil action brought by a person listed in Section 693.013 who
did not object before the removal of corneal tissue, a medical examiner,
justice of the peace, or eye bank official is not liable for damages on
a theory of civil recovery based on a contention that the person's
consent was required before the corneal tissue could be removed.

(b) Chapter 104, Civil Practice and Remedies Code, applies to a justice
of the peace, medical examiner, and their personnel who remove, permit
removal, or deny removal of corneal tissue under this subchapter as if
the justice of the peace, medical examiner, and their personnel were
state officers or employees.

Acts 1989, 71st Leg., ch. 678, Sec. 1, eff. Sept. 1, 1989.

Note: This information includes legislation enacted through the 75th
Congress. The 76th session of the Texas Legislature has concluded. The
State of Texas has not yet made the new codes available to the public.
Until they do, search the bill text for any changes or amendments.

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.

############ http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############



From: Terry S. Singeltary Sr. (216-119-138-149.ipset18.wt.net)
Subject: Trial Contact Lenses and RE-USE in the U.S. & CJD, no threat says FDA???
Date: October 7, 2000 at 9:19 am PST

Subject: Trial Contact Lenses and RE-USE in the U.S. & CJD, no threat says FDA???
Date: Sat, 7 Oct 2000 10:27:03 -0700
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de

######### Bovine Spongiform Encephalopathy #########

Greetings List Members,

It just never ceases to amaze me, that the FDA and the rest of
the different political governmental bodies that are suppose to
protect us, but instead, choose to protect their best interest$
the corporate industries that donate all the cash$ there has been
plenty of warning and tests to prove of some sort of infectivity
in the eyes. the fda speaks of no test for the tears, well hell, there
is no test that will detect it period, but yet you still die from it.
does not mean it is not there. when will they wake up? sporadic
CJD is coming from somewhere and they had better start looking as to
where it is coming from. this is just more typical B.S.eee. please
read the ignorance, below....

thank you,
Terry S. Singeltary Sr., Bacliff, Texas USA


Subject: 09-018 - gsc - flounder@wt.net - concern of CJD transmission
with trial contact lenses
Date: Fri, 06 Oct 2000 14:49:24 -0400
From: "Clark, Geoffrey S."
To: "'flounder@wt.net'"
CC: "Warburton, Karen" ,
"CDRH Small Manu. Assistance"

Terry S. Singeltary Sr.:

I have discussed your concerns with our Device Evaluation staff who have
provided the following information:

The risk of CJD transmission through the use of trial (fitting) contact
lenses is extremely low and at present unmeasureable. There have been
no documented cases of CJD transmission via a contact lens or contact
lens solution. It is highly unlikely that the CJD agent would be
present on the surface of the cornea or present in the tears of an
infected person. Additionally, the use of trial lens sets has been
declining in the US over the past 10 years as the soft contact lens
market has shifted to lenses dispensed in non-reusable blister packs.
Therefore, a formal recommendation against the use of trial lenses
because of potential CJD transmission is not appropriate at this time.

Please feel free to contact me if I can be of additional assistance.

=<:"Geoff Clark gsc@cdrh.fda.gov from PC 5074275; Room 130H <> (HFZ-220)
1350 Piccard Dr., Rockville, MD 20850-4307
800.638.2041x122
fax.301.443.8818




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



From: Winston, F. Blix
Sent: Tuesday, September 05, 2000 5:00 PM
To: Clark, Geoffrey S.
Subject: 09-018 - flounder@wt.net
Geoff,

This came into the DSMA account. Would you please respond?

Thanks, Blix

-----Original Message-----
From: WEBO@CDRH.FDA.GOV [SMTP:WEBO@CDRH.FDA.GOV]

Sent: Friday, September 01, 2000 9:27 AM
To: DSMA@CDRH.FDA.GOV
Subject: DSMA Email Form Response

Name: Terry S. Singeltary Sr.
Phone Number: Na
Fax Number: Na
Email Address: flounder@wt.net
Mailing Address:
P.O.
Box 42
Bacliff, Texas USA 77518

Questions/Comments:
P990072
*In relation to human Transmissible Spongiform Encephalopathy and
Contact Lens

i think it would be to everyone's best interest, "IF" the practice of
"RE-USING" _display_ contact lens in the commercial aspect takes place
in the U.S., this practice must be stopped. Please allow me to explain.
In the U.K., the practice of having display of different colors of
contact lens on display, for the consumer to try on, and see how they
look with the different colors. These contact lens were then re-used
over and over. No standard cleaning cleaning solution and or
auto-claving procedure will kill the TSE agent. This is known fact.
Plus, the U.K. has 'BANNED' this practice due to vCJD and sCJD (if i am
not mistaken), but regardless, both can transmit the TSE agent. I will
not waste my time trying to explain this in this box, will post a few
URLS and you will see what i speak of if you care.
But the eyes, brain, pituitary are the most infectious parts, of an
infective species. Trust me, i know what i speak of.......

thank you,
Terry S. Singeltary SR.

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

ISSUE 1490

Thursday 24 June 1999

CJD alert over contact lenses
By David Brown, Agriculture Editor

PEOPLE risk catching the human form of mad cow disease from re-used
contact lenses, scientists warned the Government yesterday.
They urged the Department of Health to stop opticians re-using trial
lenses among their clients to help prevent further outbreaks of the new
variant Creutzfeldt-Jakob disease which has killed 41 people so far.

The warning came from the Spongiform Encephalopathies Advisory
Committee, the independent team of scientists advising the Government on
BSE and CJD. Ministers are expected to ban the re-use of these lenses as
a precaution, which could mean higher prices for consumers.

In a statement, the committee said: "Any potential risk is probably very
low, but the committee felt strongly that the Department of Health
should encourage opticians to adopt, as a matter of best practice, the
single use of trial lenses followed by safe disposal." Sir John
Pattison, the committee's chairman, said it was surprised to learn that
it was common practice among opticians to try the same contact lenses on
several clients.

It was known that the classical variety of CJD, the kind which was known
before the new variant (vCJD) was announced in 1996 and linked to BSE,
had been spread in the past by transplants of infected corneas.

The committee noted that the eyes are directly connected to the brain,
the main seat of BSE and CJD. The warning applied to vCJD and the
classical variety of the fatal brain disease.


http://www.telegraph.co.uk:80/et?ac=003588399104365&rtmo=0iJRs00q&atmo=tttttttd&pg=/et/99/6/24/ncjd24.html



JOURNAL OF NEUROLOGY

MARCH 26, 2003

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States

Email Terry S. Singeltary:

flounder@wt.net

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?


http://www.neurology.org/cgi/eletters/60/2/176#535




Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009

August 10, 2009

Greetings,

I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. North America seems to have the most species with documented Transmissible Spongiform Encephalopathy's, most all of which have been rendered and fed back to food producing animals and to humans for years. If you look at the statistics, sporadic CJD seems to be rising in the USA, and has been, with atypical cases of the sCJD. I find deeply disturbing in the year of 2009, that Human Transmissible Spongiform Encephalopathy of any strain and or phenotype, of all age groups, and I stress all age groups, because human TSE's do not know age, and they do not know borders. someone 56 years old, that has a human TSE, that has surgery, can pass this TSE agent on i.e. friendly fire, and or passing it forward, and there have been documented nvCJD in a 74 year old. Remembering also that only sporadic CJD has been documented to transmit via iatrogenic routes, until recently with the 4 cases of blood related transmission, of which the origin is thought to be nvCJD donors. However most Iatrogenic CJD cases are nothing more than sporadic CJD, until the source is proven, then it becomes Iatrogenic. An oxymoron of sorts, because all sporadic CJD is, are multiple forms, or strains, or phenotypes of Creutzfeldt Jakob Disease, that the route and source and species have not been confirmed and or documented. When will the myth of the UKBSEnvCJD only theory be put to bed for good. This theory in my opinion, and the following there from, as the GOLD STANDARD, has done nothing more than help spread this agent around the globe. Politics and money have caused the terrible consequences to date, and the fact that TSEs are a slow incubating death, but a death that is 100% certain for those that are exposed and live long enough to go clinical. once clinical, there is no recourse, to date. But, while sub-clinical, how many can one exposed human infect? Can humans exposed to CWD and scrapie strains pass it forward as some form of sporadic CJD in the surgical and medical arenas? why must we wait decades and decades to prove this point, only to expose millions needlessly, only for the sake of the industries involved? would it not have been prudent from the beginning to just include all TSE's, and rule them out from there with transmission studies and change policies there from, as opposed to doing just the opposite? The science of TSE's have been nothing more than a political circus since the beginning, and for anyone to still believe in this one strain, one group of bovines, in one geographical location, with only one age group of human TSE i.e. nvCJD myth, for anyone to believe this today only enhances to spreading of these human and animal TSE's. This is exactly why we have been in this quagmire.

The ones that believe that there is a spontaneous CJD in 85%+ of all cases of human TSE, and the ones that do not believe that cattle can have this same phenomenon, are two of the same, the industry, and so goes the political science aspect of this tobacco and or asbestos scenario i.e. follow the money. I could go into all angles of this man made nightmare, the real facts and science, for instance, the continuing rendering technology and slow cooking with low temps that brewed this stew up, and the fact that THE USA HAD THIS TECHNOLOGY FIRST AND SHIPPED IT TO THE U.K. SOME 5 YEARS BEFORE THE U.S. STARTED USING THE SAME TECHNOLOGY, to save on fuel cost. This is what supposedly amplified the TSE agent via sheep scrapie, and spread via feed in the U.K. bovine, and other countries exporting the tainted product. BUT most everyone ignores this fact, and the fact that the U.S. has been recycling more TSE, from more species with TSEs, than any other country documented, but yet, it's all spontaneous, and the rise in sporadic CJD in the U.S. is a happenstance of bad luck ??? I respectfully disagree. To top that all off, the infamous BSE-FIREWALL that the USDA always brags about was nothing more than ink on paper, and I can prove this. YOU can ignore it, but this is FACT (see source, as late as 2007, in one recall alone, some 10,000,000 MILLION POUNDS OF BANNED MAD COW FEED WENT OUT INTO COMMERCE TO BE FED OUT, and most was never recovered. This was banned blood laced, meat and bone meal. 2006 was a banner year for banned mad cow protein going into commerce in the U.S. (see source of FDA feed ban warning letter below). I stress that the August 4, 1997 USA mad cow feed ban and this infamous BSE firewall, was nothing more than ink on paper, it was never enforceable.

I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route. This would further have to be broken down to strain of species and then the route of transmission would further have to be broken down. Accumulation and Transmission are key to the threshold from sub- clinical to clinical disease, and key to all this, is to stop the amplification and transmission of this agent, the spreading of, no matter what strain. In my opinion, to continue with this myth that the U.K. strain of BSE one strain TSE in cows, and the nv/v CJD one strain TSE humans, and the one geographical location source i.e. U.K., and that all the rest of human TSE are just one single strain i.e. sporadic CJD, a happenstance of bad luck that just happens due to a twisted protein that just twisted the wrong way, IN 85%+ OF ALL HUMAN TSEs, when to date there are 6 different phenotypes of sCJD, and growing per Gambetti et al, and that no other animal TSE transmits to humans ??? With all due respect to all Scientist that believe this, I beg to differ. To continue with this masquerade will only continue to spread, expose, and kill, who knows how many more in the years and decades to come. ONE was enough for me, My Mom, hvCJD i.e. Heidenhain Variant CJD, DOD 12/14/97 confirmed, which is nothing more than another mans name added to CJD, like CJD itself, Jakob and Creutzfeldt, or Gerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE, named after another human. WE are only kidding ourselves with the current diagnostic criteria for human and animal TSE, especially differentiating between the nvCJD vs the sporadic CJD strains and then the GSS strains and also the FFI fatal familial insomnia strains or the ones that mimics one or the other of those TSE? Tissue infectivity and strain typing of the many variants of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ...

please see history, and the ever evolving TSE science to date ;


Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009


http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html




Thursday, November 05, 2009

Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification


http://creutzfeldt-jakob-disease.blogspot.com/2009/11/incidence-and-spectrum-of-sporadic.html




Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

Brian S. Appleby, MD; Kristin K. Appleby, MD; Barbara J. Crain, MD, PhD; Chiadi U. Onyike, MD, MHS; Mitchell T. Wallin, MD, MPH; Peter V. Rabins, MD, MPH

Background: The classic Creutzfeldt-Jakob disease (CJD), Heidenhain, and Oppenheimer-Brownell variants are sporadic CJD (sCJD) phenotypes frequently described in the literature, but many cases present with neuropsychiatric symptoms, suggesting that there may be additional sCJD phenotypes.

Objective: To characterize clinical, diagnostic, and molecular features of 5 sCJD variants.

Design: Retrospective analysis.

Setting: The Johns Hopkins and Veterans Administration health care systems.

Participants: Eighty-eight patients with definite or probable sCJD.

Main Outcome Measures: Differences in age at onset, illness progression, diagnostic test results, and molecular subtype.

Results: The age at onset differed among sCJD variants (P=.03); the affective variant had the youngest mean age at onset (59.7 years). Survival time (P
.001) and the time to clinical presentation (P=.003) differed among groups. Patients with the classic CJD phenotype had the shortest median survival time from symptom onset (66 days) and those who met criteria for the affective sCJD variant had the longest (421 days) and presented to clinicians significantly later (median time from onset to presentation, 92 days; P=.004). Cerebrospinal fluid analyses were positive for 14-3-3 protein in all of the affective variants, regardless of illness duration. Periodic sharp-wave complexes were not detected on any of the electroencephalography tracings in the Oppenheimer-Brownell group; basal ganglia hyperintensity was not detected on brain magnetic resonance imaging in this group either. All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

Conclusions: The classic CJD phenotype and the Heidenhain, Oppenheimer-Brownell, cognitive, and affective sCJD variants differ by age at disease onset, survival time, and diagnostic test results. Characteristics of these 5 phenotypes are provided to facilitate further clinicopathologic investigation that may lead to more reliable and timely diagnoses of sCJD.

Arch Neurol. 2009;66(2):208-215

snip...

COMMENT

snip...see full text ;


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/characteristics-of-established-and.html




TSS