Thursday, March 8, 2018

Familial human prion diseases associated with prion protein mutations Y226X and G131V are transmissible to transgenic mice expressing human prion protein

Thursday, March 8, 2018

NIAID scientists assess transmission risk of familial human prion diseases to mice

Image of prion protein fibrils Prion protein fibrils. 

NIAID 

What 

Familial human prion diseases are passed within families and are associated with 34 known prion protein mutations. To determine whether three of the unstudied mutations are transmissible, scientists from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, exposed research mice to brain samples from three people who died from a familial prion disease. After observing the mice for about two years, they found two of the mutations, Y226X and G131V, are transmissible.

Perhaps more interesting, the Y226X patient sample had previously been preserved in formaldehyde for three days, embedded in wax, and dried on glass specimen slides for several years before being rehydrated for the study. Yet, the sample infected four of eight mice.

The finding illustrates the hardiness of prion infectivity and the potential risks associated with prion transmission, potentially through surgery, blood transfusion or tissue donation. Samples for the other two mutations studied were taken from frozen brain tissue that was thawed.

Prion diseases originate when normally harmless prion protein molecules become abnormal and gather in clusters and filaments in the human body and brain. The reasons for this process are not fully understood. Familial human prion diseases include genetic Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, and fatal familial insomnia. All are fatal and thus far untreatable. Of the 34 known prion protein mutations, scientists now have tested 13 for transmissibility, identifying nine as transmissible to monkeys or mice.

Article B Race et al. Familial human prion diseases associated with prion protein mutations Y226X and G131V are transmissible to transgenic mice expressing human prion protein. Acta Neuropathologica Communications DOI: 10.1186/s40478-018-0516-2 (2018).

Who Bruce Chesebro, M.D., chief of the NIAID Laboratory of Persistent Viral Diseases, is available to comment on this study.

Contact To schedule interviews, please contact Ken Pekoc, (301) 402-1663, kpekoc@niaid.nih.gov (link sends e-mail).

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website. 

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health®

###



Familial human prion diseases associated with prion protein mutations Y226X and G131V are transmissible to transgenic mice expressing human prion protein 

Brent Race,corresponding author1 Katie Williams,1 Andrew G. Hughson,1 Casper Jansen,2 Piero Parchi,3,4 Annemieke J. M. Rozemuller,5,6 and Bruce Chesebro corresponding author1 


Abstract Human familial prion diseases are associated with mutations at 34 different prion protein (PrP) amino acid residues. However, it is unclear whether infectious prions are found in all cases. Mutant PrP itself may be neurotoxic, or alternatively, PrP mutation might predispose to spontaneous formation of infectious PrP isoforms. Previous reports demonstrated transmission to animal models by human brain tissue expressing 7 different PrP mutations, but 3 other mutations were not transmissible. In the present work, we tested transmission using brain homogenates from patients expressing 3 untested PrP mutants: G131V, Y226X, and Q227X. Human brain homogenates were injected intracerebrally into tg66 transgenic mice overexpressing human PrP. Mice were followed for nearly 800 days.

From 593 to 762 dpi, 4 of 8 mice injected with Y226X brain had PrPSc detectable in brain by immunostaining, immunoblot, and PrP amyloid seeding activity assayed by RT-QuIC. From 531 to 784 dpi, 11 of 11 G131V-injected mice had PrPSc deposition in brain, but none were positive by immunoblot or RT-QuIC assay. In contrast, from 529 to 798 dpi, no tg66 mice injected with Q227X brain had PrPSc or PrP amyloid seeding activity detectable by these methods. Y226X is the only one of 4 known PrP truncations associated with familial disease which has been shown to be transmissible. This transmission of prion infectivity from a patient expressing truncated human PrP may have implications for the spread and possible transmission of other aggregated truncated proteins in prion-like diseases such as Alzheimer’s disease, Parkinson’s disease and tauopathies.

snip...

Detection of prion infectivity in prion disease-affected human brain has also been studied by injection of human patient brain into susceptible animals. Transmission of sporadic, iatrogenic and variant forms of CJD has been demonstrated previously []. However, results of transmission experiments using familial prion disease brain have been more variable. Transmission experiments using human CNS tissue of familial prion disease patients have been done with ten of the 34 PrP mutations known to be associated with prion disease. In these experiments, seven mutations gave positive transmissions to rodents or primates. These included GSS-associated mutations (P102L, A117V, F198S) [], FFI mutation (D178N with 129 MM) [] and familial CJD mutations (D178N with 129VV, E200K, V210I, M232R) []. In contrast, no transmission was reported for mutations P105L, Y145X, or Y163X []. It remains unclear whether these negative cases lacked any prion infectivity or were the result of low infectivity levels in the brain regions analyzed or the use of less sensitive host animals for the transmissions. Interestingly, two of these negative transmission cases involved patients with a mutation which created a stop codon resulting in PrP truncation (Y145X and Y163X), suggesting that PrP truncations might not generate spontaneous prion infectivity in vivo in humans.
In the present study, we performed transmission experiments using brain tissue of human patients expressing three previously untested PrP mutations (Y226X, Q227X, and G131V) []. Tg66 transgenic mice expressing human PrP at a level 8–16-fold higher than physiological levels [] were used as recipients. Interestingly, two of these human patients had PrP mutations resulting in a stop codon at positions 226 or 227, thus lacking the final 5–6 amino acid residues of PrP as well as the C-terminal glycophosphatidylinositol (GPI) anchor group. Thus, the mutant PrP in these two patients was remarkably similar to the anchorless PrP expressed in tg44 transgenic mice [], which showed severe cerebral amyloid angiopathy (CAA) after scrapie infection, similar to the Y226X patient. In this work, we observed transmission to tg66 mice by tissue from the Y226X patient starting at 593 dpi, and possible transmission of G131V starting at 531 dpi. In contrast, no transmission by Q227X was seen by 798 dpi which was the latest time-point analyzed. Y226X is the first human PrP mutant associated with PrP truncation which has been found to be transmissible.
snip...
In summary, the present results bring to 13 the number of PrP point mutations associated with familial prion disease which have been tested for transmission. Of these, 9 mutations have showed evidence for transmission to primates or rodents. PrP Y226X is the first PrP mutation encoding a truncated PrP molecule which was transmissible. In contrast, the other truncated PrP mutant tested here, Q227X, showed no evidence for transmission which was similar to two other truncation mutants previously tested by others. These differences in transmission might be due to the influence of specific protein folding structural factors on generation of infectivity, or alternatively, they might be due to biological statistical variation in the quantity of prion infectivity present in the brain samples tested.
see full text;


FRIDAY, JANUARY 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what if ???
Greetings Friends, Neighbors, and Colleagues,
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what if ???
Confucius is confused again.
I was just sitting and thinking about why there is no genetic link to some of these TSE prion sGSS, sFFi, and it’s really been working on my brain, and then it hit me today.
what if, vpspr, sgss, sffi, TSE prion disease, was a by-product from iatrogenic gss, ffi, familial type prion disease ???
it could explain the cases of no genetic link to the gss, ffi, familial type prion disease, to the family.
sporadic and familial is a red herring, in my opinion, and underestimation is spot on, due to the crude prehistoric diagnostic procedures and criteria and definition of a prion disease.
I say again, what if, iatrogenic, what if, with all these neurological disorders, with a common denominator that is increasingly showing up in the picture, called the prion.
I urge all scientist to come together here, with this as the utmost of importance about all these neurological disease that are increasingly showing up as a prion mechanism, to put on the front burners, the IATROGENIC aspect and the potential of transmission there from, with diseases/disease??? in question.
by definition, could they be a Transmissible Spongiform Encephalopathy TSE prion type disease, and if so, what are the iatrogenic chances of transmission?
this is very important, and should be at the forefront of research, and if proven, could be a monumental breakthrough in science and battle against the spreading of these disease/diseases.


sporadic CJD, along with new TSE prion disease in humans, of which the young are dying, of which long duration of illness from onset of symptoms to death have been documented, only to have a new name added to the pot of prion disease i.e. sporadic GSS, sporadic FFI, and or VPSPR. I only ponder how a familial type disease could be sporadic with no genetic link to any family member? when the USA is the only documented Country in the world to have documented two different cases of atypical H-type BSE, with one case being called atypical H-G BSE with the G meaning Genetic, with new science now showing that indeed atypical H-type BSE is very possible transmitted to cattle via oral transmission (Prion2014). sporadic CJD and VPSPR have been rising in Canada, USA, and the UK, with the same old excuse, better surveillance. You can only use that excuse for so many years, for so many decades, until one must conclude that CJD TSE prion cases are rising. a 48% incease in CJD in Canada is not just a blip or a reason of better surveillance, it is a mathematical rise in numbers. More and more we are seeing more humans exposed in various circumstance in the Hospital, Medical, Surgical arenas to the TSE Prion disease, and at the same time in North America, more and more humans are becoming exposed to the TSE prion disease via consumption of the TSE prion via deer and elk, cattle, sheep and goats, and for those that are exposed via or consumption, go on to further expose many others via the iatrogenic modes of transmission of the TSE prion disease i.e. friendly fire. I pondered this mode of transmission via the victims of sporadic FFI, sporadic GSS, could this be a iatrogenic event from someone sub-clinical with sFFI or sGSS ? what if?



The occurrence of the disease in a patient who had contact with cases of familial C.J.D., but was not genetically related, has been described in Chile (Galvez et al., 1980) and in France (Brown et al., 1979b). In Chile the patient was related by marriage, but with no consanguinity, and had social contact with subsequently affected family members for 13 years before developing the disease. The contact case in France also married into a family in which C.J.D. was prevalent and had close contact with an affected member. In neither instance did the spouse of the non-familial case have the disease. The case described in this report was similarly related to affected family members and social contact had occurred for 20 years prior to developing C.J.D. If contact transmission had occurred, the minimum transmission period would be 11 years. Contact between sporadic cases has not been described and it is remarkable that possible contact transmissions have all been with familial cases. No method of transmission by casual social contact has been suggested.

***The occurrence of contact cases raises the possibility that transmission in families may be effected by an unusually virulent strain of the agent.

snip...see full text here;




TUESDAY, DECEMBER 12, 2017 

Creutzfeldt Jakob Disease CJD National Prion Disease Pathology Surveillance Center Cases Examined to December 14, 2017






Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan.

*** This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.

*** It also suggests a similar cause or source for atypical BSE in these countries. ***

see page 176 of 201 pages...tss

*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply;

Wednesday, July 15, 2015

Additional BSE TSE prion testing detects pathologic lesion in unusual brain location and PrPsc by PMCA only, how many cases have we missed?

***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.

***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.

*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***

Posted by Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT


Alzheimer's disease or TSE Prion ???


Re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy 

>>> The only tenable public line will be that "more research is required’’ <<< 

>>> possibility on a transmissible prion remains open<<< 

O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ? 

Re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy 

Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015) 

snip...see full Singeltary Nature comment here; 

Alzheimer's disease

let's not forget the elephant in the room. curing Alzheimer's would be a great and wonderful thing, but for starters, why not start with the obvious, lets prove the cause or causes, and then start to stop that. think iatrogenic, friendly fire, or the pass it forward mode of transmission. think medical, surgical, dental, tissue, blood, related transmission. think transmissible spongiform encephalopathy aka tse prion disease aka mad cow type disease... 

Commentary: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy





Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease 

*** Singeltary comment PLoS *** 

Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ? 

Posted by flounder on 05 Nov 2014 at 21:27 GMT 


IN CONFIDENCE

5 NOVEMBER 1992

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES

[9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication. 

There are also results to be made available shortly 

(1) concerning a farmer with CJD who had BSE animals, 

(2) on the possible transmissibility of Alzheimer’s and 

(3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.]




snip...see full Singeltary Nature comment here at bottom ; 

re-Evidence for human transmission of amyloid-? pathology and cerebral amyloid angiopathy Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)


I would kindly like to comment on the Nature Paper, the Lancet reply, and the newspaper articles.

First, I applaud Nature, the Scientist and Authors of the Nature paper, for bringing this important finding to the attention of the public domain, and the media for printing said findings.

Secondly, it seems once again, politics is getting in the way possibly of more important Transmissible Spongiform Encephalopathy TSE Prion scientific findings. findings that could have great implications for human health, and great implications for the medical surgical arena. but apparently, the government peer review process, of the peer review science, tries to intervene again to water down said disturbing findings.

where have we all heard this before? it?s been well documented via the BSE Inquiry. have they not learned a lesson from the last time?

we have seen this time and time again in England (and other Country?s) with the BSE mad cow TSE Prion debacle.

That ?anonymous' Lancet editorial was disgraceful. The editor, Dick Horton is not a scientist.

The pituitary cadavers were very likely elderly and among them some were on their way to CJD or Alzheimer's. Not a bit unusual. Then the recipients ? who got pooled extracts injected from thousands of cadavers ? were 100% certain to have been injected with both seeds. No surprise that they got both diseases going after thirty year incubations.

That the UK has a "system in place to assist science journalists" to squash embargoed science reports they find ?alarming? is pathetic.

Sounds like the journalists had it right in the first place: ?Alzheimer?s may be a transmissible infection? in The Independent to ?You can catch Alzheimer?s? in The Daily Mirror or ?Alzheimer?s bombshell" in The Daily Express

if not for the journalist, the layperson would not know about these important findings.

where would we be today with sound science, from where we were 30 years ago, if not for the cloak of secrecy and save the industry at all cost mentality?

when you have a peer review system for science, from which a government constantly circumvents, then you have a problem with science, and humans die.

to date, as far as documented body bag count, with all TSE prion named to date, that count is still relatively low (one was too many in my case, Mom hvCJD), however that changes drastically once the TSE Prion link is made with Alzheimer?s, the price of poker goes up drastically.

so, who makes that final decision, and how many more decades do we have to wait?

the iatrogenic mode of transmission of TSE prion, the many routes there from, load factor, threshold from said load factor to sub-clinical disease, to clinical disease, to death, much time is there to spread a TSE Prion to anywhere, but whom, by whom, and when, do we make that final decision to do something about it globally? how many documented body bags does it take? how many more decades do we wait? how many names can we make up for one disease, TSE prion?

Professor Collinge et al, and others, have had troubles in the past with the Government meddling in scientific findings, that might in some way involve industry, never mind human and or animal health.

FOR any government to continue to circumvent science for monetary gain, fear factor, or any reason, shame, shame on you.

in my opinion, it?s one of the reasons we are at where we are at to date, with regards to the TSE Prion disease science i.e. money, industry, politics, then comes science, in that order.

greed, corporate, lobbyist there from, and government, must be removed from the peer review process of sound science, it?s bad enough having them in the pharmaceutical aspect of healthcare policy making, in my opinion.

my mother died from confirmed hvCJD, and her brother (my uncle) Alzheimer?s of some type (no autopsy?). just made a promise, never forget, and never let them forget, before I do.

I kindly wish to remind the public of the past, and a possible future we all hopes never happens again. ...



2012

Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?

Background

Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease have both been around a long time, and was discovered in or around the same time frame, early 1900’s. Both diseases are incurable and debilitating brain disease, that are in the end, 100% fatal, with the incubation/clinical period of the Alzheimer’s disease being longer (most of the time) than the TSE prion disease. Symptoms are very similar, and pathology is very similar.

Methods

Through years of research, as a layperson, of peer review journals, transmission studies, and observations of loved ones and friends that have died from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant Creutzfelt Jakob Disease CJD.

Results

I propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation disease, and that Alzheimer’s is Transmissible, and is a threat to the public via the many Iatrogenic routes and sources. It was said long ago that the only thing that disputes this, is Alzheimer’s disease transmissibility, or the lack of. The likelihood of many victims of Alzheimer’s disease from the many different Iatrogenic routes and modes of transmission as with the TSE prion disease.

Conclusions

There should be a Global Congressional Science round table event set up immediately to address these concerns from the many potential routes and sources of the TSE prion disease, including Alzheimer’s disease, and a emergency global doctrine put into effect to help combat the spread of Alzheimer’s disease via the medical, surgical, dental, tissue, and blood arena’s. All human and animal TSE prion disease, including Alzheimer’s should be made reportable in every state, and Internationally, WITH NO age restrictions. Until a proven method of decontamination and autoclaving is proven, and put forth in use universally, in all hospitals and medical, surgical arena’s, or the TSE prion agent will continue to spread. IF we wait until science and corporate politicians wait until politics lets science _prove_ this once and for all, and set forth regulations there from, we will all be exposed to the TSE Prion agents, if that has not happened already.

end...tss

Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?

source references ...end...tss 

Hello Nicole,

by all means, please do use my poster. but I thought this was already taken care of, and I could not attend for my poster presentation, therefore, it was not going to be presented. I have some health issues and could not make the trip.

please see old correspondence below...

From: Nicole Sanders Sent: Tuesday, April 10, 2012 5:37 PM To: Terry S. Singeltary Sr. Subject: RE: re-submission

Dear Terry,

The decline of proposal number 30756 is registered in the system. Thank you for your consideration.

Best Regards,

Nicole

Nicole Sanders

Senior Specialist, Membership & Conference Programming

______________________________________


From: xxxx 

To: Terry Singeltary 

Sent: Saturday, December 05, 2009 9:09 AM 

Subject: 14th ICID - abstract accepted for 'International Scientific Exchange'

Your preliminary abstract number: 670

Dear Mr. Singeltary,

On behalf of the Scientific Committee, I am pleased to inform you that your abstract

'Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009'

WAS accepted for inclusion in the INTERNATIONAL SCIENTIFIC EXCHANGE (ISE) section of the 14th International Congress on Infectious Diseases. Accordingly, your abstract will be included in the "Intl. Scientific Exchange abstract CD-rom" of the Congress which will be distributed to all participants.

Abstracts accepted for INTERNATIONAL SCIENTIFIC EXCHANGE are NOT PRESENTED in the oral OR poster sessions.

Your abstract below was accepted for: INTERNATIONAL SCIENTIFIC EXCHANGE

#0670: Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009

Author: T. Singeltary; Bacliff, TX/US

Topic: Emerging Infectious Diseases Preferred type of presentation: International Scientific Exchange

This abstract has been ACCEPTED.

#0670: Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009

Authors: T. Singeltary; Bacliff, TX/US

Title: Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009

Body: Background

An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.

Methods

12 years independent research of available data

Results

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.

Conclusion

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. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries.

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.

Keywords: Transmissible Spongiform Encephalopathy Creutzfeldt Jakob Disease Prion

page 114 ;

http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf

http://www.isid.org/14th_icid/

http://www.isid.org/publications/ICID_Archive.shtml

http://ww2.isid.org/Downloads/IMED2009_AbstrAuth.pdf

Tuesday, December 12, 2017 

Neuropathology of iatrogenic Creutzfeldt–Jakob disease and immunoassay of French cadaver-sourced growth hormone batches suggest possible transmission of tauopathy and long incubation periods for the transmission of Abeta pathology

http://tauopathies.blogspot.com/2017/12/neuropathology-of-iatrogenic.html

WEDNESDAY, NOVEMBER 1, 2017 

Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies


Tuesday, December 12, 2017 

Neuropathology of iatrogenic Creutzfeldt–Jakob disease and immunoassay of French cadaver-sourced growth hormone batches suggest possible transmission of tauopathy and long incubation periods for the transmission of Abeta pathology


SUNDAY, MARCH 4, 2018 

Can Aβ Seeds Be Transferred During Neurosurgery?



Diagnosis and Reporting of Creutzfeldt-Jakob Disease 

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA Diagnosis and Reporting of Creutzfeldt-Jakob Disease 

To the Editor: 

In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally. 

Terry S. Singeltary, Sr Bacliff, Tex 

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. 



Tracking spongiform encephalopathies in North America

Xavier Bosch

Published: August 2003


Summary;

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.”

49-year-old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease (CJD). So he decided to gather hundreds of documents on transmissible spongiform encephalopathies (TSE) and realised that if Britons could get variant CJD from bovine spongiform encephalopathy (BSE), Americans might get a similar disorder from chronic wasting disease (CWD) the relative of mad cow disease seen among deer and elk in the USA. Although his feverish search did not lead him to the smoking gun linking CWD to a similar disease in North American people, it did uncover a largely disappointing situation.

Singeltary was greatly demoralised at the few attempts to monitor the occurrence of CJD and CWD in the USA. Only a few states have made CJD reportable. Human and animal TSEs should be reportable nationwide and internationally, he complained in a letter to the Journal of the American Medical Association (JAMA 2003; 285: 733). "I hope that the CDC does not continue to expect us to still believe that the 85% plus of all CJD cases which are sporadic are all spontaneous, without route or source."

Until recently, CWD was thought to be confined to the wild in a small region in Colorado. But since early 2002, it has been reported in other areas, including Wisconsin, South Dakota, and the Canadian province of Saskatchewan. Indeed, the occurrence of CWD in states that were not endemic previously increased concern about a widespread outbreak and possible transmission to people and cattle.

To date, experimental studies have proven that the CWD agent can be transmitted to cattle by intracerebral inoculation and that it can cross the mucous membranes of the digestive tract to initiate infection in lymphoid tissue before invasion of the central nervous system. Yet the plausibility of CWD spreading to people has remained elusive.

Part of the problem seems to stem from the US surveillance system. CJD is only reported in those areas known to be endemic foci of CWD. Moreover, US authorities have been criticised for not having performed enough prionic tests in farm deer and elk.

Although in November last year the US Food and Drug Administration issued a directive to state public-health and agriculture officials prohibiting material from CWD-positive animals from being used as an ingredient in feed for any animal species, epidemiological control and research in the USA has been quite different from the situation in the UK and Europe regarding BSE.

"Getting data on TSEs in the USA from the government is like pulling teeth", Singeltary argues. "You get it when they want you to have it, and only what they want you to have."

Norman Foster, director of the Cognitive Disorders Clinic at the University of Michigan (Ann Arbor, MI, USA), says that "current surveillance of prion disease in people in the USA is inadequate to detect whether CWD is occurring in human beings"; adding that, "the cases that we know about are reassuring, because they do not suggest the appearance of a new variant of CJD in the USA or atypical features in patients that might be exposed to CWD. However, until we establish a system that identifies and analyses a high proportion of suspected prion disease cases we will not know for sure". The USA should develop a system modelled on that established in the UK, he points out.

Ali Samii, a neurologist at Seattle VA Medical Center who recently reported the cases of three hunters "two of whom were friends" who died from pathologically confirmed CJD, says that "at present there are insufficient data to claim transmission of CWD into humans"; adding that "[only] by asking [the questions of venison consumption and deer/elk hunting] in every case can we collect suspect cases and look into the plausibility of transmission further". Samii argues that by making both doctors and hunters more aware of the possibility of prions spreading through eating venison, doctors treating hunters with dementia can consider a possible prion disease, and doctors treating CJD patients will know to ask whether they ate venison.

CDC spokesman Ermias Belay says that the CDC "will not be investigating the [Samii] cases because there is no evidence that the men ate CWD-infected meat". He notes that although "the likelihood of CWD jumping the species barrier to infect humans cannot be ruled out 100%" and that "[we] cannot be 100% sure that CWD does not exist in humans& the data seeking evidence of CWD transmission to humans have been very limited". 




26 March 2003 

Terry S. Singeltary, retired (medically) CJD WATCH 

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? 



2001 FDA CJD TSE Prion Singeltary Submission 



 *** U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001 



2 January 2000 British Medical Journal U.S. 

Scientist should be concerned with a CJD epidemic in the U.S., as well 



15 November 1999 British Medical Journal hvCJD in the USA * BSE in U.S. 



Sunday, February 25, 2018 

PRION ROUND TABLE CONFERENCE 2018 MAY, 22-25 A REVIEW



Tuesday, December 12, 2017 

Neuropathology of iatrogenic Creutzfeldt–Jakob disease and immunoassay of French cadaver-sourced growth hormone batches suggest possible transmission of tauopathy and long incubation periods for the transmission of Abeta pathology



SUNDAY, MARCH 4, 2018 

Can Aβ Seeds Be Transferred During Neurosurgery?



TUESDAY, MARCH 6, 2018 

Transmissible Spongiform Encephalopathy TSE Prion Chronic Wasting Disease CWD Cervids Zoonosis Update



Sunday, February 25, 2018 

PRION ROUND TABLE CONFERENCE 2018 MAY, 22-25 A REVIEW






DECEMBER 14, 2017, 20 YEARS POST DOD MOM HEIDENHAIN VARIANT CREUTZFELDT JAKOB DISEASE HVCJD DECEMBER 14, 1997, JUST MADE A PROMISE TO MOM, AND YOU DON'T BREAK PROMISES WITH YOUR MOM, NEVER FORGET, AND NEVER LET THEM FORGET...

wasted days and wasted nights...Freddy Fender

TERRY S. SINGELTARY SR.

Terry S. Singeltary Sr. Bacliff, Texas USA 77518 <flounder9@verizon.net