Wednesday, April 15, 2015

KURU Transmissible Spongiform Encephalopthy TSE Prion Disease

KURU Transmissible Spongiform Encephalopthy TSE Prion Disease


*** Kuru Video


Kuru: The Science and The Sorcery




*** Scrapie Video

https://histodb11.usz.ch/Images/videos/video-011/video-011.html


*** Human Mad Cow Video

https://histodb11.usz.ch/Images/videos/video-009/video-009.html


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




2014


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


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


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


snip...




Monday, October 10, 2011


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


snip...


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


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


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


snip...






Thursday, August 12, 2010


Seven main threats for the future linked to prions


First threat


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


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


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


Second threat


snip...




*** Creutzfeldt-Jakob Disease Public Health Crisis VIDEO










Tuesday, December 16, 2014


Evidence for zoonotic potential of ovine scrapie prions


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


Abstract


Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human ​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.


Subject terms: Biological sciences• Medical research At a glance




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


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


snip...


R. BRADLEY




Suspect symptoms


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


28 Mar 01 Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.


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


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


2001


Suspect symptoms


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


28 Mar 01


Like lambs to the slaughter


31 March 2001


by Debora MacKenzie Magazine issue 2284.


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


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


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


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


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


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


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


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


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


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


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


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


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




Thursday, March 20, 2014


CHRONIC WASTING DISEASE CWD TSE PRION OF CERVID AND THE POTENTIAL FOR HUMAN TRANSMISSION THEREFROM 2014




Tuesday, July 01, 2014


*** CHRONIC WASTING DISEASE CWD TSE PRION DISEASE, GAME FARMS, AND POTENTIAL RISK FACTORS THERE FROM ***




Thursday, July 03, 2014


*** How Chronic Wasting Disease is affecting deer population and what’s the risk to humans and pets? ***




Thursday


CWD TO HUMANS, AND RISK FACTORS THERE FROM (see latest science)


Tuesday, November 04, 2014


*** Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011




Friday, January 30, 2015


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




Sunday, April 12, 2015


*** Research Project: Transmission, Differentiation, and Pathobiology of Transmissible Spongiform Encephalopathies 2014 Annual Report ***




Saturday, April 11, 2015


*** ISU veterinary researchers study retinal scans as early detection method for mad cow disease




Sunday, November 23, 2014


*** Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European ***




Monday, November 3, 2014


USA CJD TSE PRION UNIT, TEXAS, SURVEILLANCE UPDATE NOVEMBER 2014


National Prion Disease Pathology Surveillance Center Cases Examined1 (October 7, 2014)


***6 Includes 11 cases in which the diagnosis is pending, and 19 inconclusive cases;


***7 Includes 12 (11 from 2014) cases with type determination pending in which the diagnosis of vCJD has been excluded.


***The sporadic cases include 2660 cases of sporadic Creutzfeldt-Jakob disease (sCJD),


***50 cases of Variably Protease-Sensitive Prionopathy (VPSPr)


***and 21 cases of sporadic Fatal Insomnia (sFI).




Thursday, January 15, 2015


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




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


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


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


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


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


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


Saturday, January 17, 2015


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




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




Tuesday, November 04, 2014


Towards an Age-Dependent Transmission Model of Acquired and Sporadic Creutzfeldt-Jakob Disease




Thursday, January 22, 2015


Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to disease etiology?






Sunday, July 06, 2014


Dietary Risk Factors for Sporadic Creutzfeldt-Jakob Disease: A Confirmatory Case-Control Study


Conclusions—The a priori hypotheses were supported.


*Consumption of various meat products may be one method of transmission of the infectious agent for sCJD.




PLEASE REMEMBER ;


The Akron, Ohio-based CJD Foundation said the Center for Disease Control revised that number in October of 2004 to about one in 9,000 CJD cases per year in the population group age 55 and older.


HAVE YOU GOT YOUR CJD QUESTIONNAIRE ASKING REAL QUESTIONS PERTAINING TO ROUTE AND SOURCE OF THE TSE AGENT THAT KILLED YOUR LOVED ONE ???


if not, why not...


Friday, November 30, 2007


CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION






Friday, January 10, 2014


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






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


Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014




Singeltary comment ;




Saturday, December 13, 2014


Terry S. Singeltary Sr. Publications TSE prion disease


Diagnosis and Reporting of Creutzfeldt-Jakob Disease


Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA


snip...





TSS

Monday, October 28, 2013

A Kiss of a Prion: New Implications for Oral Transmissibility

 we are (in my opinion), exposed to the TSE prion in so many different ways in every day life, the potential for exposure and then becoming infected via taking care of a loved one with TSE prion disease, in my opinion risk factor there from is minimal, if proper precautions are taken, and even if they were not, the chance of becoming infected from a kiss, or casual contact is low, but I do not think it is zero, actually, far from it. I put this all together for a documentation of the known facts to date, of the potential casual human to human transmission. I did not put it together to scare anyone. with aerosol transmission of the TSE prion a reality now, infectivity in urine and feces and transmission there from being reality now with the TSE prion disease, I don’t see how anyone can rule _out_ the potential for transmission of the TSE prion via a kiss (a vehicle for transmission of the TSE prion via saliva), or even for a cut or open wound (all a cut is and transmission there from, is an crude inoculation of sorts, and inoculation has been proven to be an efficient mode of transmission for the TSE prion disease), even the eye, from either one of the body fluids now that how proven to be infections. I can’t see why we have such safety protocols for laboratory workers working with the TSE prion disease, but yet the same officials will say it’s o.k. for the public, friends, and or family members to do just the opposite with their loved ones when succumbing to the CJD TSE prion disease. don’t get me wrong, I did it too, and would probably do it again as far as kissing my mom. but science is science, and the transmission studies speak for themselves with the bodily fluids. simply put, which is all I was saying, we can’t say never, and or that none of these cases to date, have not been, and or will not be, a potential vehicle for transmission. I believe, and this is my opinion, that more concern for casual transmission with body fluids and materials there from, should be put forth to families with their loved ones, and I think that the safety protocols there from should be revised, to match that of the laboratory settings. again, this is my opinion. your opinion, and or others here, may read the same science and feel different out the findings. ...take care, kind regards, terry

SUBSTANCE DATA SHEET

HUMAN PRION AGENTS


FOR USE IN RESEARCH LABORATORIES


SECTION I - INFECTIOUS AGENT


Name: Creutzfeldt-Jakob agent, Kuru agent


Synonym or Cross Reference:: Subacute spongiform encephalopathy, Creutzfeldt-Jakob disease (CJD), Kuru, Transmissible Spongiform Encephalopathy (TSE).


Characteristics: Filterable, self-replicating agent, slow infectious pathogen, prion protein (PrP)


SECTION II - RECOMMENDED PRECAUTIONS


Containment Requirements: Biosafety level 3 facilities, practices and containment equipment for activities involving these agents; also listed under biosafety level 2 with special precautions; level of containment will depend on the nature of the manipulations and the amount of sera, bio/necropsy materials handled


Protective Clothing: Gown and gloves when handling potentially infectious materials; eye protection may also be indicated


Other Precautions: Extreme care must be taken to avoid accidental autoinoculation or other parenteral inoculations of infectious tissues and fluids


SECTION III - HANDLING INFORMATION


Spills: Allow any potential aerosols to settle; wearing protective clothing, gently cover spill with paper towel and apply 1N sodium hydroxide, starting at perimeter and working towards the center; allow sufficient contact time (1 hour) before clean up


Disposal: Decontaminate before disposal; steam sterilization (132·C for 1 hour), disinfection with 1N sodium hydroxide for 1 hour, incineration


Storage: In sealed containers that are appropriately labeled




The main precaution to be taken by laboratorians working with prion-infected or contaminated material is to avoid accidental puncture of the skin.3 Persons handling contaminated specimens should wear cut-resistant gloves if possible. If accidental contamination of unbroken skin occurs, the area should be washed with detergent and abundant quantities of warm water (avoid scrubbing); brief exposure (1 minute to 1N NaOH or a 1:10 dilution of bleach) can be considered for maximum safety.6 Additional guidance related to occupational injury are provided in the WHO infection control guidelines.6 Unfixed samples of brain, spinal cord, and other tissues containing human prions should be processed with extreme care in a BSL-2 facility utilizing BSL-3 practices.


Bovine Spongiform Encephalopathy Although the eventual total number of variant CJD cases resulting from BSE transmission to humans is unknown, a review of the epidemiological data from the United Kingdom indicates that BSE transmission to humans is not efficient.9 The most prudent approach is to study BSE prions at a minimum in a BSL-2 facility utilizing BSL-3 practices. When performing necropsies on large animals where there is an opportunity that the worker may be accidentally splashed or have contact with high-risk materials (e.g., spinal column, brain) personnel should wear full body coverage personal protective equipment (e.g., gloves, rear closing gown and face shield). Disposable plasticware, which can be discarded as a dry regulated medical waste, is highly recommended. Because the paraformaldehyde vaporization procedure does not diminish prion titers, BSCs must be decontaminated with 1N NaOH and rinsed with water. HEPA filters should be bagged out and incinerated. Although there is no evidence to suggest that aerosol transmission occurs in the natural disease, it is prudent to avoid the generation of aerosols or droplets during the manipulation of tissues or fluids and during the necropsy of experimental animals. It is further strongly recommended that impervious gloves be worn for activities that provide the opportunity for skin contact with infectious tissues and fluids.




The main precaution to be taken when working with prion-infected or contaminated material is to avoid puncture of the skin. If accidental contamination of skin occurs, the area is swabbed with In sodium hydroxide (NaOH) for 5 minutes and then washed with copious amounts of water. Unfixed samples of brain, spinal cord, and other tissues containing human prions should be processed with extreme care at BSL 3.


Prions are characterized by extreme resistance to conventional inactivation procedures including irradiation, boiling, dry heat, and chemicals (formalin, betapropiolactone, alcohols). Sterilization of rodent brain extracts with high titers of prions requires autoclaving at 132C for 4.5 hours. Denaturing organic solvents such as phenol or chaotropic reagents such as guanidine isothiocyanate or alkali such as NaOH can also be used for sterilization. Disposable plasticware, which can be discarded as a dry waste, is highly recommended.


Although there is no evidence to suggest that aerosol transmission occurs in the natural disease, it is prudent to avoid the generation of aerosols or droplets during the manipulation of tissues or fluids and during the necropsy of experimental animals. Formaldehyde-fixed and paraffin-embedded tissues, especially of the brain, remain infectious. Some investigators recommend that formalin-fixed tissues from suspected cases of prion disease be immersed for 30 min in 96% formic acid or phenol before histopathologic processing, but such treatment may severely distort the microscopic neuropathology.




another interesting aspect of the TSE prion disease is KURU ;


Figure 25. All cooking. including that of human flesh from diseased kinsmen. was done in pits with steam made by pouring water over the hot stones, or cooked in bamboo cylinders in the hot ashes. Children participated in both the butchery and the handling of cooked meat, rubbing their soiled hands in their armpits or hair, and elsewhere on their bodies. They rarely or never washed. Infection with the kuru virus was most probably through the cuts and abrasions of the skin. or from nose-picking, rye (eye...tss) rubbing, or mucosal injury.



These detailed descriptions will be published elsewhere but have reaffirmed the oral histories of endocannibalism in the Fore recorded previously12,22–24 and that this practice ceased abruptly at the time of Australian administrative control over the kuru areas. Although isolated events might have occurred for a few years after this prohibition, we are confident that new exposures of individuals to kuru at mortuary feasts would not have occurred after 1960. Not only have no cases of kuru been recorded in people born after 1959 (and only nine were recorded in those born after 1956); but also all the 11 last recorded cases of kuru that we report here were born before 1950. If any source of infection remained, whether from surreptitious cannibalism, possible ground contam-ination with human prions at sites where food was prepared, or other lateral routes, we would expect individuals born after this period to have kuru—especially since children are thought to have had shorter incubation periods than adults. However, no such cases have been observed. Additionally, although a fraction of hamster-adapted scrapie prions have been shown to survive in soil for at least 3 years,25 the mortuary feast practices (during which the entire body would be consumed) were undertaken so that any substantial contamination of soil would not have occurred, and traditional bamboo knives and leaf plates were burned after the feast. Furthermore, no clusters of kuru cases, as seen earlier in the epidemic,26 have been recorded for many years....




Kuru: The Science and the Sorcery


Special Jury Prize Winner, Pacific International Documentary Film Festival 2011.


This is the true story of one of the most incredible and challenging medical detective stories of the 20th Century; a history of human tragedy, adventure and discovery. It is the story of the Fore, a Papuan community immersed in cannibalistic mortuary practices and sorcery in one of the most remote regions on the planet, and the tragic disease that threatened to wipe out their entire population.


In 1961, a young Australian medical researcher, Michael Alpers, puts up his hand to work on a new and strange disease in the Eastern Highlands of Papua New Guinea. There, he teams up with an American outer, Dr Carleton Gajdusek, who has been in the local Fore region since 1957. For Michael it is the beginning of a lifelong obsession.


Together, they are amidst a major epidemic. It is killing over 200 people a year with devastating effects. It mainly targets women and children. The local people, the Fore, call the disease kuru, their word for shivering. They believe it is caused by sorcery.


Michael and Carleton are baffled by the disease. There are no scientific disciplines to guide them as they attempt to unravel its mysteries. By pure chance, a link is made to a strange transmissible animal disease in sheep, Scrapie. The two kuru researchers embark on a 10-year experiment to see if the fatal degenerative brain disease in humans could be transmissible like Scrapie.


The decision is made to perform an autopsy on a kuru victim and inoculate the kuru material into a chimpanzee. Kigea, ayoung girl in the village is identified as being in the early stages of kuru. Kigea’s family, gives Michael permission to perform an autopsy upon her death.


A brain sample taken from Kigea after her death is flown to the USA and injected into a chimpanzee called Daisy. While Michael follows the progress of the transmission experiment, he starts to collate all the recorded data on kuru and begins to suspect cannibalism as the cause of the spreadof the disease.


Within two years, he diagnoses Daisy with kuru. This is a defining moment. It confirms kuru is transmissible and can cross the species barrier. The revelation, together with epidemiological data collated with anthropologist Shirley Lindenbaum, links the Fore’s mortuary feasts (consumption of dead relatives) to the transmission of kuru. Cannibalism is the cause, and its origin is linked to a rare disease called Creutzfeldt Jakob Disease(CJD), but the story of kuru is far from over.


The infecting agent is the first new pathogen – prions – to be discovered in over 100 years. Research results in two Nobel prizes: it’s discoveries turning scientific understanding upside down, causing rifts in the beliefs ofthe science community.


Then Mad Cow Disease (Bovine Spongiform Encephalopathy or BSE) reared its head in the mid 1980s, and 10 years later the human variant CJD. All eyes turned to kuru, the only model of a prion epidemic in human populations. Many unknowns still surround prion diseases: there is no cure for kuru, or any of the prion diseases. The effects are devastating and unprecedented incubation periods can extend beyond 50 years.


Michael is the key and heart to this story, providing unique access to the Fore people, and the world’s other leading authorities on the matter; including Americans Prof. DC Gajdusek (Nobel Prize 1976), Prof. Stan Prusiner (Nobel Prize 1997), Prof Shirley Lindenbaum (Anthropologist) and British Prof. John Collinge (Director, MRC Prion Unit, UK).


Kuru: The Science and the Sorcery combines history, science and anthropology to tell a unique and ongoing ‘history of science’ documentary spanning five decades. It intertwines the thinking of great minds, locally and internationally, to reveal how this rare disease in the remote highlands of PNG exploded to international attention and how Prion research has now revealed we are all descendants of a remote past of cannibal practices.






Kuru: The Science and the Sorcery Australian scientist Michael Alpers dedicated over 50 years to researching Kuru, an obscure and incurable brain disease unique to the Fore people of New Guinea. Kuru was once thought to be a psychosomatic illness, an infection, a genetic disorder, even a sorcerer's curse, but Alpers' findings pointed to cannibalism as the culprit. Yet a recent discovery has proven to be even more disturbing: the malady is linked to mad cow disease and its human equivalent, variant CJD. With a decades-long incubation period, could a larger outbreak be on its way?









human flesh taste very sweet





KURU EPIDEMIOLOGICAL PATROLS





Michael Alpers





First Reports





People of the Kuru region part 1


boy playing with animal bladder, blowing it up like a balloon. ...





People of the Kuru region part 2





Monday, November 19, 2012


Prion in Saliva of Bovine Spongiform Encephalopathy–Infected Cattle




please see full text ;



Sunday, October 27, 2013

A Kiss of a Prion: New Implications for Oral Transmissibility



kind regards,
terry



Wednesday, November 18, 2009

A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure

A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure


Simon Mead, M.R.C.P., Jerome Whitfield, M.A., Mark Poulter, B.Sc., Paresh Shah, Ph.D., James Uphill, B.Sc., Tracy Campbell, B.Sc., Huda Al-Dujaily, B.Sc., Holger Hummerich, Ph.D., Jon Beck, B.Sc., Charles A. Mein, Ph.D., Claudio Verzilli, Ph.D., John Whittaker, Ph.D., Michael P. Alpers, F.R.S., and John Collinge, F.R.S.


ABSTRACT

Background Kuru is a devastating epidemic prion disease that affected a highly restricted geographic area of the Papua New Guinea highlands; at its peak, it predominantly affected adult women and children of both sexes. Its incidence has steadily declined since the cessation of its route of transmission, endocannibalism.

Methods We performed genetic and selected clinical and genealogic assessments of more than 3000 persons from Eastern Highland populations, including 709 who participated in cannibalistic mortuary feasts, 152 of whom subsequently died of kuru.

Results Persons who were exposed to kuru and survived the epidemic in Papua New Guinea are predominantly heterozygotes at the known resistance factor at codon 129 of the prion protein gene (PRNP). We now report a novel PRNP variant — G127V — that was found exclusively in people who lived in the region in which kuru was prevalent and that was present in half of the otherwise susceptible women from the region of highest exposure who were homozygous for methionine at PRNP codon 129. Although this allele is common in the area with the highest incidence of kuru, it is not found in patients with kuru and in unexposed population groups worldwide. Genealogic analysis reveals a significantly lower incidence of kuru in pedigrees that harbor the protective allele than in geographically matched control families.

Conclusions The 127V polymorphism is an acquired prion disease resistance factor selected during the kuru epidemic, rather than a pathogenic mutation that could have triggered the kuru epidemic. Variants at codons 127 and 129 of PRNP demonstrate the population genetic response to an epidemic of prion disease and represent a powerful episode of recent selection in humans.

Source Information

From the Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology (S.M., J. Whitfield, M.P., P.S., J.U., T.C., H.A.-D., H.H., J.B., M.P.A., J.C.); the Genome Centre, Barts and the London Queen Mary's School of Medicine and Dentistry, John Vane Science Centre (C.A.M.); and the Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine (C.V., J. Whittaker) — all in London; Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province, Papua New Guinea (J. Whitfield, M.P.A.); and the Centre for International Health, Curtin University, Perth, WA, Australia (M.P.A.).

Address reprint requests to Dr. Collinge at the Department of Neurodegenerative Disease, Institute of Neurology, Queen Sq., London WC1N 3BG, United Kingdom, or at j.collinge@prion.ucl.ac.uk.


http://content.nejm.org/cgi/content/short/361/21/2056



Brain disease “resistance gene” could offer insights into CJD19 November 2009 A community in Papua New Guinea that suffered a major epidemic of a CJD-like fatal brain disease called kuru has developed strong genetic resistance to the disease, according to new research by Medical Research Council (MRC) scientists.

Kuru is a fatal prion disease, similar to CJD in humans and BSE in animals, and is geographically unique to an area in Papua New Guinea. In the mid 20th Century, an epidemic of kuru devastated a population in the Eastern Highlands of Papua New Guinea. The infection was passed on at mortuary feasts, where mainly women and children consumed their deceased relatives as a mark of respect and mourning. This practice was banned and ceased in the late 1950s.

Scientists from the MRC Prion Unit, a national centre of excellence in prion diseases, assessed over 3000 people from the affected and surrounding Eastern Highland populations, including 709 who had participated in cannibalistic mortuary feasts, 152 of whom subsequently died of kuru. They discovered a novel and unique variation in the prion protein gene called G127V in people from the Purosa valley region where kuru was most rife.

This gene mutation, which is found nowhere else in the world, seems to offer high or even complete protection against the development of kuru and has become frequent in this area through natural selection over recent history, in direct response to the epidemic. This is thought be perhaps the strongest example yet of recent natural selection in humans.

Lead author Professor John Collinge, Director of the MRC Prion Unit said:

“It’s absolutely fascinating to see Darwinian principles at work here. This community of people has developed their own biologically unique response to a truly terrible epidemic. The fact that this genetic evolution has happened in a matter of decades is remarkable. Kuru comes from the same disease family as CJD so the discovery of this powerful resistance factor opens up new areas for research taking us closer to understanding, treating and hopefully preventing a range of prion diseases.”

The study “A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure”, which began in 1996, will be published in the New England Journal of Medicine on 19 November 2009.

ENDS

Notes to editors 1. Study available on request.

2. For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including the first antibiotic penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk

3. Prion diseases or transmissible spongiform encephalopathies (TSEs) belong to group of progressive conditions that affect the nervous system in humans and animals. In humans, prion diseases impair brain function, causing memory changes, personality changes, a decline in intellectual function (dementia), and problems with movement that worsen over time. They are fatal conditions. Familial prion diseases of humans include classic Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS) fatal insomnia (FI) and Kuru.

4. Kuru was restricted to the Fore linguistic groups and their immediate neighbours which whom they intermarried. It was the practice in the Fore society for kinship groups to consume deceased relatives at mortuary feasts, a practice that resulted in human-to-human prion transmission. On the whole, men and children over 8 years of age did not participate in the feast, with the result that kuru at its peak predominantly affected women and children. As recorded in oral history the first cases appeared in the early 20th century and thereafter the number of cases increased in incidence. A peak annual mortality of more than 2% was recorded in some villages. Some villages became largely devoid of young women. More information on the Papua New Guinea Institute of Medical Research is available here www.pngimr.org.pg.

5. The study was lead by the Medical Research Council Prion Unit, and involved scientists from the University College London Institute of Neurology; Papua New Guinea Institute of Medical Research; and Curtin University Australia. Other institutions participating; the Genome Centre, Barts the London Queen Mary’s School of Medicine and Dentistry; London School of Hygiene and Tropical Medicine.

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


http://www.mrc.ac.uk/Newspublications/News/MRC006502





November 19, 2009

Brain-eating tribe enriches understanding of mad cow disease

Mark Henderson, Science Editor Recommend? A cannibalistic ritual in which the brains of dead tribespeople were eaten by their relatives has triggered one of the most striking examples of rapid human evolution on record, scientists have discovered.

In the middle of the 20th century the Fore tribe of the Eastern Highlands province of Papua New Guinea was devastated by a CJD-like disease called kuru, which was passed on by mortuary feasts in which the brains of the dead were consumed.

Although the practice was banned in the 1950s and kuru has disappeared, it has left an imprint on the tribe’s DNA. Research has now identified a genetic mutation unique to the Fore that protects against the brain disease and which has spread swiftly through the population by natural selection.

As the mutation confers high or almost complete resistance to kuru, carriers have a survival advantage and have had more descendants. About 8 per cent of people from the Purosa Valley region, where kuru hit hardest, now have the gene, which is unknown anywhere else in the world.

Related Links Daniel Gajdusek New wave of mad cow disease feared What the cannibals taught us The findings, from a team led by Simon Mead, of the Medical Research Council Prion Unit at University College London, show how quickly human evolution can respond to new environmental pressures.

They are described today in The New England Journal of Medicine as scientists prepare to celebrate the 150th anniversary of the publication of Charles Darwin’s On the Origin of Species on Tuesday.

Professor John Collinge, the director of the prion unit, said: “It’s absolutely fascinating to see Darwinian principles at work here. This community of people have developed their own biologically unique response to a truly terrible epidemic. The fact that this genetic evolution has happened in a matter of decades is remarkable.”

The research is also significant because it promises to shed light on the rogue prion proteins that cause Creutzfeldt-Jakob disease (vCJD), the human form of mad cow disease.

Dr Mead said: “It isn’t going to lead to a drug tomorrow but it would improve our background understanding of how prion diseases work and how they might be prevented.”

Oral histories provided by elderly members of the Fore tribe suggest that kuru emerged in the early 20th century and developed into a serious epidemic with an annual mortality rate of more than 2 per cent in some villages.

It mainly affected women and children, who would eat the remains of dead relatives. Kuru disappeared when cannibal rituals were stopped in the 1950s under the influence of missionaries.

In the new study scientists analysed the DNA of more than 3,000 people from affected and unaffected parts of the Eastern Highlands, including 709 who had taken part in cannibalistic rituals and 152 who had died of kuru.

The variant in the prion protein gene, called G127V, appears to have emerged about 1800 and then became advantageous with the arrival of kuru.

Dr Mead said that the variant would have spread rapidly for two reasons: “First, if you’re a carrier you’re resistant to the disease. More subtly, it also had benefits in terms of the relatives eaten. If you were in a family protected against kuru and ate auntie’s brain you were less likely to be eating an infected brain.”

In the genes

Sickle-cell anaemia This genetic disease is more common among African and Mediterranean people because the gene responsible also confers resistance to malaria

Blood groups People with blood group O are more vulnerable to cholera but less susceptible to malaria, spread by mosquitoes

HIV There is evidence that a variant of a gene called CCR5-32, which offers resistance against HIV, is increasing in frequency in Africa

Lactose tolerance Common in ethnic groups with a strong pastoral tradition such as North Europeans and East Africans

Skin colour Natural selection favours dark skins at equatorial latitudes for cancer protection, but pale skins at high latitudes, because they allow greater production of vitamin D

Source: Times database


http://www.timesonline.co.uk/tol/news/science/biology_evolution/article6922057.ece




Tuesday, July 28, 2009

The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt–Jakob disease and scrapie agents


http://kuru-tse.blogspot.com/2009/07/kuru-infectious-agent-is-unique.html




Kuru in the 21st century—an acquired human prion disease Thu Jun 22, 2006 19:44 70.110.82.186

The Lancet 2006; 367:2068-2074

DOI:10.1016/S0140-6736(06)68930-7

Kuru in the 21st century—an acquired human prion disease with very long incubation periods John Collinge a , Jerome Whitfield a b, Edward McKintosh a, John Beck a, Simon Mead a, Dafydd J Thomas a and Michael P Alpers a c

Summary Background Kuru provides the principal experience of epidemic human prion disease. Its incidence has steadily fallen after the abrupt cessation of its route of transmission (endocannibalism) in Papua New Guinea in the 1950s. The onset of variant Creutzfeldt-Jakob disease (vCJD), and the unknown prevalence of infection after the extensive dietary exposure to bovine spongiform encephalopathy (BSE) prions in the UK, has led to renewed interest in kuru. We investigated possible incubation periods, pathogenesis, and genetic susceptibility factors in kuru patients in Papua New Guinea.

Methods We strengthened active kuru surveillance in 1996 with an expanded field team to investigate all suspected patients. Detailed histories of residence and exposure to mortuary feasts were obtained together with serial neurological examination, if possible.

Findings We identified 11 patients with kuru from July, 1996, to June, 2004, all living in the South Fore. All patients were born before the cessation of cannibalism in the late 1950s. The minimum estimated incubation periods ranged from 34 to 41 years. However, likely incubation periods in men ranged from 39 to 56 years and could have been up to 7 years longer. PRNP analysis showed that most patients with kuru were heterozygous at polymorphic codon 129, a genotype associated with extended incubation periods and resistance to prion disease.

Interpretation Incubation periods of infection with human prions can exceed 50 years. In human infection with BSE prions, species-barrier effects, which are characteristic of cross-species transmission, would be expected to further increase the mean and range of incubation periods, compared with recycling of prions within species. These data should inform attempts to model variant CJD epidemiology.

Affiliations

a. MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, London WC1N 3BG, UK b. Papua New Guinea Institute of Medical Research, Goroka, EHP, Papua New Guinea c. Centre for International Health, Curtin University, Perth, Australia

Correspondence to: Prof John Collinge

http://www.thelancet.com/journals/lancet/article/PIIS0140673606689307/abstract


TSS

Listen to The Lancet This week's audio summary discusses an Article entitled "Kuru in the 21st century - an acquired human prion disease with very long incubation periods". Also covered is a Lecture assessing climate change and its impact on health, and an Editorial about the roll-out of cervical cancer vaccines worldwide. >>

http://www.thelancet.com/webfiles/images/clusters/thelancet/audio/24June2006.mp3


further into this study;

Discussion

The early clinical, epidemiological, and anthropological study of kuru; the recognition of its neuropathological, and then causal parallels to ovine scrapie;20 and then crucially, the experimental transmission of the disease

to primates,21 originated the concept of the human transmissible spongiform encephalopathies, which was followed in turn by the eventual unifying concept of the mammalian prion diseases. However, in addition to the central historical importance of kuru, study of the end-stage of this epidemic offers a unique opportunity to study the variables of a near-complete epidemic of human prion disease. In particular, recognition of the incubation periods possible after natural prion infection in people is important in providing an insight (from actual case histories rather than from mathematical models) into the probable span of the vCJD epidemic in the UK. Although estimation of kuru incubation periods early in the epidemic was difficult, and the timing of the actual infecting event for an individual can rarely be determined, the abrupt and permanent interruption of the source of infection, endocannibalism, in the late 1950s, has progressively allowed recognition of an enormous span of possible incubation periods, at its shortest extreme bracketed by the rare onset of disease in children as young as 5 years and extending up to (and perhaps beyond) the incubations covering more than half a century, as we describe here.In our field studies, we have interviewed many individuals who participated in traditional mortuary feasting or who described the participation of family members from the preceding generation. These detailed descriptions will be published elsewhere but have reaffirmed the oral histories of endocannibalism in the Fore recorded previously12,22–24 and that this practice ceased abruptly at the time of Australian administrative control over the kuru areas. Although isolated events might have occurred for a few years after this prohibition, we are confident that new exposures of individuals to kuru at mortuary feasts would not have occurred after 1960. Not only have no cases of kuru been recorded in people born after 1959 (and only nine were recorded in those born after 1956); but also all the 11 last recorded cases of kuru that we report here were born before 1950. If any source of infection remained, whether from surreptitious cannibalism, possible ground contam-ination with human prions at sites where food was prepared, or other lateral routes, we would expect individuals born after this period to have kuru—especially since children are thought to have had shorter incubation periods than adults. However, no such cases have been observed. Additionally, although a fraction of hamster-adapted scrapie prions have been shown to survive in soil for at least 3 years,25 the mortuary feast practices (during which the entire body would be consumed) were undertaken so that any substantial contamination of soil would not have occurred, and traditional bamboo knives and leaf plates were burned after the feast. Furthermore, no clusters of kuru cases, as seen earlier in the epidemic,26 have been recorded for many years. We have also reviewed the assertion that maternal transmission of kuru did not occur, and saw no evidence for maternal transmission from kuru archives, interviews of colleagues who have practised medicine in the Fore, or local oral history. Again, any possible vertical route of kuru transmission would have resulted in the presence of kuru in children born after 1960, especially since kuru was common in women of childbearing age; no such cases have occurred.With respect to extrapolation of incubation periods of BSE prion infection in people, we should recognise that the kuru epidemic arose from intraspecies recycling of infectious prions. However, transmission of prions between different mammalian species is associated with a species barrier, which is better described as a transmission barrier, because of the importance of within-species prion strain type, in addition to species-specific differences in its determination.27 The biological effects of such a barrier are: extended mean incubation period; increased spread of incubation periods in individual animals; and reduced attack rate (in which only a fraction of inoculated animals will succumb), by comparison with the 100% mortality generally associated with within-species inoculation with high-titre infectivity. Incubation periods approaching the natural lifespan of the inoculated species are often seen in such primary cross-species transmissions of prions. Second and subsequent passage of prions within the new species is always associated with adaptation involving a considerable shortening of the mean and spread of incubation periods and high or total lethality to high-titre inocula. Thus, estimation of the range of possible incubation periods in human BSE infection needs superimposition of the effect of a transmission barrier onto these findings of natural human incubation periods. The mean incubation period for kuru has been estimated to be around 12 years,27 with a similar estimate in iatrogenic CJD associated with the use of human-cadaver-derived pituitary growth hormone.28 As shown here, maximum incubation periods in kuru can exceed 50 years. The transmission barrier of BSE between cattle and human beings is unknown and cannot be directly measured. However, the cattle-to-mouse barrier for BSE has been well characterised experimentally by comparative endpoint titration. BSE prions transmit readily to laboratory mice, including after oral dosing.29 The murine LD50 (lethal dose causing 50% mortality) in C57Bl/6 mice is about 500-fold higher than that in cattle;30 this barrier also results in a three-fold to four-fold increase in mean incubation period.27 Mean incubation periods of human BSE infection of 30 years or more should therefore be regarded as possible, if not probable,27 with the longest incubation periods approaching (and perhaps exceeding) the typical human lifespan. The shortest incubation periods in kuru were estimated from the age of the youngest patients—suggesting that the shortest incubation period was Articles www.thelancet.com Vol 367 June 24, 2006 2073 4–5 years. Similarly in vCJD, although the total clinical caseload so far has been small, the youngest onsets of vCJD have been at age 12 years or above, providing an early estimate of a minimum incubation period. Furthermore, prion disease in mice follows a well-defined course with a highly distinctive and repeatable incubation time for a specific prion strain in a defined inbred mouse line. In addition to the PrP gene, a few additional genetic loci with a major effect on incubation period have been mapped.4,31,32 Human homologues of such loci could be important in human susceptibility to prion disease, both after accidental human prion exposure and after exposure to the BSE agent. By definition, patients identified so far with vCJD are those with the shortest incubation periods for BSE. These patients could have received an especially high dose of BSE prions. However, no unusual history of dietary, occupational, or other exposure to BSE has been reported from case-control studies. Because of the powerful genetic effects on incubation period in laboratory animals, vCJD patients identified could represent a distinct genetic subpopulation with unusually short incubation periods to BSE prions, with vCJD so far occurring predominantly in those individuals with short incubation time alleles at these multiple genetic loci, in addition to having the homozygous PRNP genotype of codon 129 methionine. Therefore, a human BSE epidemic may be multiphasic, and recent estimates of the size of the vCJD epidemic based on uniform genetic susceptibility could be substantial underestimations.33,34 Genes implicated in species-barrier effects, which would further increase both the mean and range of human BSE incubation periods, are also probably relevant. In this context, a human epidemic will be difficult to accurately model until such modifier loci are identified and their gene frequencies in the population can be measured.4Heterozygosity at PRNP codon 129 is a major determinant of susceptibility to and incubation time of human prion diseases.5,7,9,35 As expected, most of these recent kuru cases with extended incubation periods (eight of ten) were heterozygotes. We have reported previously that most elderly survivors of exposure to traditional mortuary feasts are heterozygous.9 Although the study included a small number of patients with kuru with long incubation periods, we saw no evidence of association with PRNP haplotype,10 HLA-DQ7,18 APOE,36 or PRND alleles.13

Contributors

J Whitfield led the field patrol team throughout the study and investigated all suspect cases; E McKintosh provided assistance during this time. J Beck and S Mead undertook the molecular genetic studies. J Collinge, M P Alpers, E McKintosh, and D J Thomas did field neurological examinations. J Collinge and M P Alpers supervised the study and drafted the manuscript. All authors contributed to and approved the final version of the manuscript. .........

snip...end...TSS

Posted by: Terry S. Singeltary Sr. July 25, 2006 07:05 PM


http://blogs.nature.com/news/blog/2006/06/cjdrelated_disease_can_incubat.html



http://kuru-tse.blogspot.com/




TSS

Tuesday, July 28, 2009

The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt–Jakob disease and scrapie agents

The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt–Jakob disease and scrapie agents

Laura Manuelidis1, Trisha Chakrabarty, Kohtaro Miyazawa, Nana-Aba Nduom, and Kaitlin Emmerling Section of Neuropathology, Yale University Medical School, 333 Cedar Street, New Haven, CT 06510 Communicated by Sheldon Penman, Massachusetts Institute of Technology, Brookline, MA, May 27, 2009 (received for review March 27, 2009)

Human sporadic Creutzfeldt–Jakob disease (sCJD), endemic sheep scrapie, and epidemic bovine spongiform encephalopathy (BSE) are caused by a related group of infectious agents. The new U.K. BSE agent spread to many species, including humans, and clarifying the origin, specificity, virulence, and diversity of these agents is critical, particularly because infected humans do not develop disease for many years. As with viruses, transmissible spongiform encephalopathy (TSE) agents can adapt to new species and become more virulent yet maintain fundamentally unique and stable identities. To make agent differences manifest, one must keep the host genotype constant. Many TSE agents have revealed their independent identities in normal mice. We transmitted primate kuru, a TSE once epidemic in New Guinea, to mice expressing normal and 8-fold higher levels of murine prion protein (PrP). High levels of murine PrP did not prevent infection but instead shortened incubation time, as would be expected for a viral receptor. Sporadic CJD and BSE agents and representative scrapie agents were clearly different from kuru in incubation time, brain neuropathology, and lymphoreticular involvement. Many TSE agents can infect monotypic cultured GT1 cells, and unlike sporadic CJD isolates, kuru rapidly and stably infected these cells. The geographic independence of the kuru agent provides additional reasons to explore causal environmental pathogens in these infectious neurodegenerative diseases.

snip...

Discussion The kuru agent stands out from the other CJD and scrapie agents here on the basis of incubation times, behavior, and neuropathology in 2 mouse genotypes. There was no evidence that it resembles or derives from sCJD. The clearly unique behavioral changes documented with each different agent in mice are compatible with the vastly different regional neuropathological changes that they induce. Additionally, whereas 15 independent sCJD isolates readily transmitted to hamsters (8), the kCJD sample did not. Remarkably, even after several prolonged 350-day serial passages in mice, the sCJD agent retained its capacity to reinfect hamsters with a short 150-day incubation and provoked the original widespread hamster lesions (8). The stability of sCJD agents, regardless of whether first passaged in multiple or in no other species, is also evident in the invariant scratching behavior and the highly restricted thalamic lesions produced in mice. The GT1 culture experiments recapitulated major kCJD and sCJD differences. Whereas sCJD produced negligible PrP-res, kCJD brain homogenates reproducibly infected and stably induced large amounts of PrP-res in GT1 cells. As in brain, kCJD did not provoke any unique agent-specific PrP-res band pattern that bred true. Rather, it showed only the standard GT1 pattern. On the basis of previous results, the GT1 PrP-res pattern confers no demonstrable change in the fundamental identity and behavior of TSE infectious agents (9, 16, 34).

Spleen studies further separated kuru and sCJD agents. The kCJD agent induced major accumulations of abnormal PrP in FDCs of the lymphoreticular system, whereas sCJD isolates provoked very few. Although different species infected with a single agent can show different levels of infectivity and pathological PrP deposits in the spleen, abnormal PrP in the spleen has important biological consequences, given the person-to-person transmission of vCJD by transfusion (11). The observation of abundant deposits in kCJD-infected mouse spleen, in addition to the infectivity of kCJD in primate spleens (31), supports transmission of kuru not only through ingestion but also via the bloodstream from wounds incurred during ritual cannibalism (1). The bloodstream is an excellent conduit for rapid and effective infection of many tissues, including the gastrointestinal tract (12, 35).

We have shown 100% transmission of the infectious kuru agent to both normal and Tg mice with WT murine PrP. Recently, kuru was transmitted to Tg mice overexpressing human PrP sequences (22) but not to normal mice. High numbers of PrP copies can enhance the development of rapid murine models, and the kCJD model here, like the vCJD model previously (11), yielded shorter incubation times than humanized PrP mice. Thus, the TSE infec- tious particle rather than the host’s PrP sequence defines crossspecies virulence. The sCJD agent is also relatively incapable of adaptive evolution in mice. Even after 8 passages, it has a very prolonged incubation time of 300 days, in contrast to kCJD and vCJD. Current and previous data do not support a conversion of homologous PrP to an infectious form, but are in accord with the proposal that host PrP is a required agent receptor that can modulate disease expression. Host receptor differences often modulate viral infection and disease progression. The kCJD and other TSE agents here maintain their fundamental identity, despite their adaptation to a new species and to monotypic cells with disparate cell-type-specific PrP bands.

The PrP-res band patterns often are presumed to encode agentspecific information, yet they are a relatively poor indicator of the biological diversity and stability of TSE agents. In the present studies, only the vCJD agent elicited a consistent PrP-res marker in different species and cell types that bred true. Eleven other independent isolates did not (11, 32). In contrast, incubation times are clearly distinctive for each agent group and nonoverlapping when both CD-1 and Tga20 values are considered. The extreme precision of incubation time with each type of agent is really quite remarkable and remains unexplained by prion theory. It also begs the question of what type of viral (nucleic acid) sequence could lead to this diversity, and this further underscores both complex and subversive interactions between these TSE agents and their hosts. The differential susceptibility of neuronal subtypes with the same PrP to the various TSE agents presents yet another conundrum for prion theory.

There are many aspects of TSE agent biology and structure that remain unresolved, but these agents clearly encode individual virus-like properties. None of these diverse biological properties can be explained parsimoniously by the prion hypothesis or by actual PrP observations. The many distinct geographic TSE agents, the local outbreak of epidemic kuru and BSE, the rare but sudden mutation or progressive selection of new virulent strains (14, 15), and the endemic perpetuation of infection only in exposed hosts (as in sheep scrapie) strongly implicate a viral structure in the environment (10). On a structural level, the presence of nucleic acid in all infectious preparations and the consistent observation of virus-like ultrastructural particles support this hypothesis. Although host PrP as well as other factors may modulate susceptibility to infection and disease phenotype, there is also no simple genetic inheritance pattern, nor evidence for a spontaneous conversion of PrP into an infectious form.

The clear distinction of kuru from western sCJD, its occurrence only in New Guinea, and the observation that Japanese CJD is limited to Asia make one suspect that additional geographic TSE isolates in the environment may be uncovered. The U.S. stopped its scrapie eradication program years ago, before comparative rodent and culture models were introduced. Since then, scrapie agents with new properties may have evolved, possibly facilitating their spread to deer in the U.S. Geographic French scrapie agents are different (31), and Europe appears to be free of U.S. cervid TSE. An understanding of the origin, relative virulence, individual properties, and molecular structure of TSE agents remains a fundamental problem and a public health issue. The distinctive biology of a wide variety of TSE agents revealed in mice and in monotypic cultures already has defined intrinsic agent properties, and simplified cultures may allow one to follow and develop ways to limit the spread of different environmental TSE agents.

Methods

snip...see full text ;



http://www.pnas.org/content/early/2009/07/23/0905825106.full.pdf+html



Sent: Monday, July 27, 2009 10:31 PM

CJD-L] [BSE-L] U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?

FINALLY, GOT IT UPLOADED !

SEE THE VIDEO NOW AT THE BOTTOM OF THE BLOG BELOW ;



http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html



Tuesday, July 21, 2009

Transmissible mink encephalopathy - review of the etiology



http://transmissible-mink-encephalopathy.blogspot.com/2009/07/transmissible-mink-encephalopathy.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



Monday, May 11, 2009

Rare BSE mutation raises concerns over risks to public health



http://bse-atypical.blogspot.com/2009/05/rare-bse-mutation-raises-concerns-over.html



Monday, June 01, 2009

Biochemical typing of pathological prion protein in aging cattle with BSE



http://bse-atypical.blogspot.com/2009/06/biochemical-typing-of-pathological.html



Sunday, June 07, 2009

L-TYPE-BSE, H-TYPE-BSE, C-TYPE-BSE, IBNC-TYPE-BSE, TME, CWD, SCRAPIE, CJD, NORTH AMERICA



http://bse-atypical.blogspot.com/2009/06/l-type-bse-h-type-bse-c-type-bse-ibnc.html



Sunday, May 10, 2009

Identification and characterization of bovine spongiform encephalopathy cases diagnosed and not diagnosed in the United States



http://bse-atypical.blogspot.com/2009/05/identification-and-characterization-of.html



Sunday, May 17, 2009

WHO WILL WATCH THE CHILDREN ? SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE



http://downercattle.blogspot.com/2009/05/who-will-watch-children.html



Saturday, April 04, 2009

An unusually presenting case of sCJD-The VV1 subtype Volume 111, Issue 3, Pages 282-291 (April 2009)



http://creutzfeldt-jakob-disease.blogspot.com/2009/04/unusually-presenting-case-of-scjdthe.html



IT seems we have come full circle from the 'ORIGINAL 10' i.e. the 1st 10 adolescents in the UKBSEnvCJD only theory. and now we find us at the 1st 10 in USA, or is it the first 10, or the tip of the iceburg, many that went undocumented ???

lets look at the full circle, to date ;



http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html



Sunday, August 10, 2008 A New Prionopathy OR more of the same old BSe and sporadic CJD



http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html



HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008

snip...

Tissue infectivity and strain typing of the many variants Manuscript 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. ...

snip...



http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html



Elsevier Editorial System(tm) for The Lancet Infectious Diseases Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary

Abstract:

TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. 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 2007. snip...

see full text 31 pages ;



http://www.regulations.gov/fdmspublic/ContentViewer?objectId=090000648027c28e&disposition=attachment&contentType=pdf



Friday, November 30, 2007

CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION



http://cjdquestionnaire.blogspot.com/



Friday, May 29, 2009

Characterization of a U.S. Sheep Scrapie Isolate with Short Incubation Time



http://scrapie-usa.blogspot.com/2009/05/characterization-of-us-sheep-scrapie.html



Wednesday, July 1, 2009

Nor98 scrapie identified in the United States J Vet Diagn Invest 21:454-463 (2009)



http://nor-98.blogspot.com/2009/07/nor98-scrapie-identified-in-united.html



Monday, June 01, 2009 Biochemical typing of pathological prion protein in aging cattle with BSE

SOMETHING TO PONDER ???

O.K. confusious asks, IF all these new atypical BSEs i.e. new strains of mad cow disease is just an 'OLD COW PRION DISEASE', why then can not the 'old human prion disease' such as the sporadic CJD, be from an 'old cow prion disease', same as the nvCJD 'young people mad cow disease' (which also happens in 74 year old), but why cannot the 'old cow prion diseases', i.e. l-BSE, h-BSE, and ibncBSE, cause the 'old people prion disease', which looks like sporadic CJD. seems that is what some of the pathology is showing ???

OH, that probably makes too much sense, and that the only answer could be that it's all just a happenstance of bad luck and or a spontaneous event, that just happens out of the clear blue sky $$$

IF this is the case, then where are all the SPONTANEOUS BSE CASES OF MAD COW DISEASE IN THE U.S.A., AND WHERE HAVE THEY BEEN BURIED IN THE USA OVER THE LAST 25 YEARS ???



http://bse-atypical.blogspot.com/2009/06/biochemical-typing-of-pathological.html



Sunday, April 12, 2009

CWD UPDATE Infection Studies in Two Species of Non-Human Primates and one Environmental reservoir infectivity study and evidence of two strains



http://chronic-wasting-disease.blogspot.com/2009/04/cwd-update-infection-studies-in-two.html



Thursday, April 03, 2008

A prion disease of cervids: Chronic wasting disease

2008 1: Vet Res. 2008 Apr 3;39(4):41

A prion disease of cervids: Chronic wasting disease

Sigurdson CJ.

snip...

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

snip...

full text ;



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



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

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

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

From: "Belay, Ermias"

To:

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

Ermias"

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

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

Dear Sir/Madam,

In the Archives of Neurology you quoted (the abstract of which was

attached to your email), we did not say CWD in humans will present like

variant CJD.

That assumption would be wrong. I encourage you to read the whole

article and call me if you have questions or need more clarification

(phone: 404-639-3091). Also, we do not claim that "no-one has ever been

infected with prion disease from eating venison." Our conclusion stating

that we found no strong evidence of CWD transmission to humans in the

article you quoted or in any other forum is limited to the patients we

investigated.

Ermias Belay, M.D.

Centers for Disease Control and Prevention

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

From:

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

To: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000146/!x-usc:mailto:rr26k@nih.gov; mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000146/!x-usc:mailto:rrace@niaid.nih.gov; mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000146/!x-usc:mailto:ebb8@CDC.GOV

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

HUNTERS

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

also,

A. Aguzzi - Chronic Wasting Disease (CWD) also needs to be addressed. Most

serious because of rapid horizontal spread and higher prevalence than BSE in

UK, up to 15% in some populations. Also may be a risk to humans - evidence

that it is not dangerous to humans is thin.



http://www.tseandfoodsafety.org/activities/bse_conference_basel_april_02/2summar



SNIP...END...TSS

Chronic Wasting Disease and Potential Transmission to Humans

Ermias D. Belay,* Ryan A. Maddox,* Elizabeth S. Williams,? Michael W. Miller,? Pierluigi Gambetti,§ and Lawrence B. Schonberger*

*Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ?University of Wyoming, Laramie, Wyoming, USA; ?Colorado Division of Wildlife, Fort Collins, Colorado, USA; and §Case Western Reserve University, Cleveland, Ohio, USA

Suggested citation for this article: Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease and potential transmission to humans. Emerg Infect Dis [serial on the Internet]. 2004 Jun [date cited]. Available from:



http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm



Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts of the United States. Although detection in some areas may be related to increased surveillance, introduction of CWD due to translocation or natural migration of animals may account for some new foci of infection. Increasing spread of CWD has raised concerns about the potential for increasing human exposure to the CWD agent. The foodborne transmission of bovine spongiform encephalopathy to humans indicates that the species barrier may not completely protect humans from animal prion diseases. Conversion of human prion protein by CWD-associated prions has been demonstrated in an in vitro cell-free experiment, but limited investigations have not identified strong evidence for CWD transmission to humans. More epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions.

snip...full text ;



http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm



please see ;



http://chronic-wasting-disease.blogspot.com/




Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

Sunday, August 3, 2008

The conference celebrating ‘The end of kuru: 50 years of research into an extraordinary disease’

The conference celebrating ‘The end of kuru: 50 years of research into an extraordinary disease’

1: Related Articles Collinge J, Alpers MP.

Introduction. Philos Trans R Soc Lond B Biol Sci. 2008 Jul 31. [Epub ahead of print] No abstract available. PMID: 18672464 [PubMed - as supplied by publisher]

http://journals.royalsociety.org/content/j104810238060l8w/fulltext.pdf


The conference celebrating ‘The end of kuru: 50 years of research into an extraordinary disease’ was held in the Kohn Room of the Royal Society, London on 11–12 October 2007. It was an extraordinary meeting that is reflected in the proceedings published in this issue of the Philosophical Transactions of the Royal Society. There were 90 participants from around the world (figure 1). The first day was devoted to reminiscences and reflections, personal and scientific, about kuru, about working and living in the kuru-affected region, and about undertaking research on kuru, from the perspectives of both medical scientists and the Fore people. On the second day, the results of contemporary research on kuru and their ever widening implications in neurodegeneration and beyond were presented, with discussions on bovine spongiform encephalopathy (BSE), its human counterpart variant Creutzfeldt– Jakob disease (vCJD) and other prion diseases. The fundamental molecular processes involved in propagation of the transmissible agent or prion are now known to be of relevance in understanding the common degenerative brain diseases (such as Alzheimer’s and Parkinson’s diseases) and possibly normal brain ageing, and may explain a range of biological phenomena as evidenced by the emergence of the field of yeast and fungal prions. Indeed, the existence of multiple strains of prions implies non-Mendelian protein-based inheritance, with major evolutionary implications. The proceedings represent the full diversity of the meeting and, unusually, include a good measure of history as well as science. This Introduction gives an account of the meeting; an account of kuru itself may be found in these proceedings in the introduction to the paper by Collinge et al. (in press). All the scientists currently working on kuru attended the conference. The two Nobel laureates in the field, D. Carleton Gajdusek and Stanley Prusiner, both participated. There were 15 Papua New Guinean participants, 12 of whom were from the Fore linguistic group, the principal sufferers from kuru since the epidemic began about a century ago. Also attending were Peter Siba, the Director of the Papua New Guinea Institute of Medical Research, which has been involved in research on kuru since its inception in 1968, Adolf Saweri, the Chairman of the Council of the Institute, who as a young doctor had worked at Okapa, the government station at the centre of the kuru-affected region (Saweri in press), and Ken Boone, a doctor in Goroka, capital of the Eastern Highlands Province, who in 2003 performed the last autopsy on a kuru patient (Boone in press). Although many of those who had worked on kuru in the field or laboratory were unable, owing to death or infirmity, to attend the conference, representatives of every era of kuru research participated. Systematic research on the disease began when Carleton Gajdusek joined Vincent Zigas in March 1957 (Gajdusek & Zigas 1957). They teamed up with Jack Baker, the patrol officer in charge of the government station at Okapa, and lived in his house (see fig. 1 in Reid in press). Vin, sadly, has died and Jack was unable to attend the meeting, but Carleton was there in full force (Gajdusek in press a,b). Other members of this team in 1957 were Lois Larkin Baker, who was unable to attend, and Lucy Hamilton Reid, who talked about her studies on the nutrition of the Fore (Reid in press). Unfortunately, no members of the Adelaide group who had worked on kuru in the early years were able to be present, though we are fortunate to have the reminiscences of J. Henry Bennett and Donald Simpson in these proceedings (Bennett in press; Simpson in press). Cyril Curtain, who contributed to the first laboratory studies on kuru (Curtain in press), took part in the meeting, which was very pleasing, though we missed the presence of Chev Kidson and the late Roy Simmons from this era of kuru research. The research workers who followed next were Robert Glasse and Shirley Lindenbaum, who studied the anthropology of the Fore people and their neighbours, and Michael Alpers. hough Bob, sadly, has died, we were pleased that Shirley could attend and contribute to the proceedings of both the days (Lindenbaum in press a,b). Of the doctors who worked at the Okapa Hospital at this time, Jonathan Hancock attended the meeting and Werner Sto¨cklin contributed to these proceedings (Sto¨cklin in press). The next group to undertake research in the field included RichardW.Hornabrook andAlexNilsson,who were unable to attend; however,Dickwas represented by Annette Beasley and we are pleased to have some reflections on kuru from himin the proceedings (Beasley in press). John Mathews, Ray Spark and Coralie Mathews all participated in the meeting. Coralie gave her own reminiscences and reflections, which were, moreover, intended to be representative of the experiences of other wives who had not only supported their scientist husbands in the field but also made their own independent relationships with the Fore people that are still affectionately remembered in the area today (Mathews, C. in press). Inamba Kivita, who had worked closely with Shirley Lindenbaum and John Mathews, was delighted to see his old friends again after so many years (Kivita in press). Richard Hornabrook became the first Director of the Papua New Guinea Institute of Medical Research and the Institute thereafter assumed the main responsibility for kuru epidemiological surveillance. John Cochrane, Margaret Cochrane, Donald Moir and

Hilary King worked in the field during the late 1960s and early 1970s. Throughout the period from 1957 to 1985, Carleton Gajdusek made many return visits to the kuru-affected region and Michael Alpers, working from Perth in Australia, made annual field excursions during the early years of the institute. They both contributed to kuru field surveillance and assisted all fieldworkers with updated printouts from the kuru database maintained at the National Institutes of Health in Bethesda by Judith Farquhar (who attended the meeting) and Steven Ono. In 1977, Michael Alpers took over as Director of the Papua New Guinea Institute of Medical Research and the field surveillance intensified; Stanley Prusiner, Robert Klitzman and Phillip Tarr attended from these years (Prusiner in press; Klitzman in press; Tarr in press). Phil Tarr conducted a village-based autopsy during his time in the field. Another autopsy was carried out by Euan Scrimgeour (in press) in Rabaul, since a Fore man came down with kuru after living there for many years and decided that he would die there (Scrimgeour in press). The four most experienced field officers from that period, Auyana Winagaiya, the late Anua Senavaiyo, Igana Alesagu and Kabina Yaragi, were unable to attend but Anua’s wife Andemba took part (Anua in press). Finally, in 1996, field activities were enhanced by a collaboration between Michael Alpers and John Collinge, initially supported by the Wellcome Trust in London (of which John was then a Principal Research Fellow), and Jerome Whitfield was recruited to work in Papua New Guinea (Collinge in press; Whitfield in press). This collaboration then formed part of the newly formed MRC Prion Unit in London from 1998, directed by John Collinge. Dafydd Thomas and Edward McKintosh were involved in the fieldwork from the MRC Unit. Henry Pako outlined the current field activities of the kuru project (Pako in press). Bridget Ogilvie, former Director of the Wellcome Trust, described the Trust’s enthusiastic and flexible attitude to the project and their early support for John Collinge. Of the neuropathologists who made the early significant observations on the histopathological features of kuru, Malcolm Fowler, E. Graeme Robertson and Elisabeth Beck had died and Igor Klatzo, who was invited to the meeting, died before it began. Their contributions were recognized by many participants during the course of the conference. As a consequence of seeing the neuropathological features of kuru at an exhibition in the Wellcome Medical Museum in London in 1959, William J. Hadlow made the seminal connection between kuru and scrapie. Though he was unable to attend, we are pleased to have his reminiscences and reflections in these proceedings (Hadlow in press). A carefully planned experiment to test the transmissibility of kuru to chimpanzees followed from Hadlow’s observations within a few years and led to a successful outcome, which was reported in 1966 by Carleton Gajdusek, C. Joseph Gibbs and Michael Alpers (Gajdusek et al. 1966). Sadly, Joe Gibbs has died but his major contribution was honoured at the meeting. This work initiated our understanding of the human transmissible spongiform encephalopathies. Subsequent work by Stanley Prusiner and others led to the unifying concept of the prion diseases. In October 2007, the epidemic of kuru may not have been entirely over but the end was certainly in sight. There was no patient with kuru in 2006 nor, as we now know, in 2007. The continuing field surveillance (Pako in press) will tell us whether we have seen the last case; at the most we can expect only one or two more. This dramatic decline from 200 deaths a year over the first 5 years of kuru investigation is a cause for celebration. To be able to celebrate the disappearance of a fatal disease, especially one so distressing in its manifestations and so well documented, is an extraordinary experience and there was a sense of elation throughout the meeting. We were uniquely privileged at this celebration to have a good representation of the people who had suffered fro the disease. The Fore participants had all lost close family members to kuru, including husbands, wives, children and mothers. Their suffering and resilience were expressed in their talks, which symbolized for the whole conference what all the people of the kuru-affected region over the span of a century (a population of approx. 40 000 at the peak of the epidemic) had endured (Bavasa in press; Mabage in press; Ombeya in press; Poki in press; Puwa in press). The burden of kuru at its peak would be equivalent in the US, for example, to well over a million deaths per annum. Moreover, since the deaths were not evenly distributed in the total affected population and since most of the deathswere in adult women, in communities of high incidence the cumulative burden of mortality affected every family: in Fore society, nobody was untouched by kuru. Many of the scientific talks also paid tribute to the Fore people and their neighbours affected by kuru. A brief film by Rob Bygott and Ben Alpers, from a larger documentary in the making, showed Fore perspectives on kuru and gave a moving portrayal of both the suffering and the resilience exhibited by dying kuru patients and their many carers. To enhance the Fore participants’ involvement in the meeting, at the end of each session, the talks and discussion were briefly summarized, with typical Papua New Guinean oratory, in Tok Pisin (by Peter Siba or Ray Spark) and Fore (by Henry Pako or Anderson Puwa). The meeting celebrated 50 years of scientific research on kuru and its many achievements. These achievements were reviewed within their historical context and their contemporary implications were analysed during the scientific presentations of the meeting. Social and behavioural studies of the Fore people, the interactions between the resident research workers and the local people, and the creative cross links that were established between disciplines during the field research were discussed in two papers, one on each day of the meeting, by Lindenbaum (in press a,b). Mathews, J. D. (in press) described how kuru had spread among the Fore, the trajectory of which has now been reasonably well established. The two factors that may have affected the probability of transmission are variations in mortuary practices (since the mode of transmission of the prion agent was through the consumption of dead relatives by the women and young children) and human genetic variation. Jerome

Whitfield described recently acquired knowledge about Fore mortuary practices and their links with Fore cosmology (Whitfield et al. in press). Much new work has been done on genetic variation and selection in relation to prion diseases, and the work on kuru, though it may not explain the local geographical spread of kuru, has produced results in population genetics that have been far-reaching and exciting (Mead et al. 2003, in press). Historical aspects of the epidemiology of kuru, including his own many significant contributions, were presented on the first day by Mathews, J. D. (in press). The sweep of the kuru epidemic from 1957 to the present, and the essential clues it has provided to solve the puzzle of kuru, were recounted on the second day by Michael Alpers from his personal experiences over the last 46 years (Alpers in press a). John Collinge discussed the contemporary implications of kuru, in particular for the vCJD, the human form of BSE (Collinge et al. in press). When the recent detailed clinical and epidemiological findings on kuru, including evidence that incubation periods after oral transmission may be greater than 50 years, are combined with new genetic information a powerful dataset is created for exploring the wider implications of kuru for other human diseases (Collinge et al. in press). Broad vistas of science were opened up by Prusiner on prions, Gajdusek (in press a) on self-propagating proteins and other entities, Per Westermark on amyloidosis (Westermark & Westermark in press) and Colin Masters on kuru and Alzheimer’s amyloid plaques (paper not available for publication). Though research on kuru has been ongoing for 50 years, only recently has it been possible to undertake molecular and biological strain typing of the prion agent of kuru. Studies at the MRC Unit have shown that kuru is caused by prion strains closely similar to those causing sporadic and iatrogenic CJD and quite distinct from that causing variant CJD (Wadsworth et al. in press). The neuropathology of the most recent autopsied case of kuru was presented in comprehensive detail by Sebastian Brandner (Brandner et al. in press). We were fortunate to have other neuropathologists at the meeting, including Byron Kakulas and Catriona McLean. Byron’s work was done during the second wave of the neuropathological study of kuru (Kakulas in press) and Catriona’s work was published during the last decade, from the examination of archival material held in Melbourne, which she has re-examined for these proceedings (McLean in press). In 1967, Gabriele Zu Rhein produced the first electron micrographs of kuru. Though she was unable to attend the meeting, she has submitted a brief account of her early findings (Zu Rhein in press). We were privileged to have at the meeting not only Carleton Gajdusek in excellent form, despite recent illhealth, but also many of his associates ranging over a wide span of years of kuru research. The oldest were Taka Gomea, Tiu Pekiyeva, Tarubi Taguse and Koiye Tasa from the earliest years of research in the field, and their reunion with Carleton was an emotional experience shared by all who were fortunate to be witnesses (Gomea in press; Pekiyeva in press; Taguse in press; Tasa in press). We sorely missed the ebullience of Vin Zigas at the meeting but were delighted that his second wife (and widow) Jettie Zigas was able to attend and speak. Of Carleton’s later associates Michael Alpers, David Asher, richard Benfante, Judith Farquhar and Robert Klitzman participated (Alpers in press b; Asher in press; Benfante in press; Farquhar in press; Klitzman in press) and Franc¸oise Cathala, though unable to be present, submitted her reminiscences (Cathala in press). Ceridwen Spark gave an animated account of Carleton’s adopted family, with its strong Melanesian connections and links to kuru research. Kuru has historical significance, not only for those who lived through the epidemic and experienced its horrors but also for historians of science (Anderson in press), particularly those interested in human behaviour, in the transiti n from a traditional mode of life to the modern world, in the relationship of scientists to the people they are studying or whose diseases they are studying, and in the international politics of science (Scragg in press). Kuru has a scientific significance that has never been lost over the years, though its focus has changed, from the challenge of an exotic new disease reaching epidemic proportions in a restricted area of the tropics, to the first human transmissible spongiform encephalopathy, which led very quickly to the transmission of Creutzfeldt–Jakob disease (Gibbs et al. 1968), to a model for multidisciplinary epidemiological enquiry, to a model for intraspecies recycling, a lesson not learned that allowed the same augmenting mechanism to cause the cattle BSE epidemic, and to a model for the oral transmission of prion disease to humans (vCJD). The intracerebral transmission to chimpanzees had an incubation period of 2 years (Gajdusek et al. 1966), which halved on first chimpanzee-to-chimpanzee passage (Gajdusek et al. 1967): these were considered extraordinarily long incubations when they were first reported. Now we have recent work demonstrating incubation periods exceeding half a century after intraspecies oral transmission, with a strong dependence on host genetics. These findings in kuru will continue to have long-standing significance for neurology, infectious disease and public health. Kuru is indeed an extraordinary disease. Many people were involved in the planning and organization of the meeting and its associated activities. These include many staff of the MRC Prion Unit (particularly Simon Mead and Caroline Potter) and other meeting participants who also hosted and guided our Fore guests. Remarkable effort was put in by Jerome Whitfield in arranging Papua New Guinea documentation and passports to enable the participation of the Fore and for accompanying them from their remote villages in the Eastern Highlands via Goroka, Port Moresby and Singapore to London and the Royal Society. Special thanks also go to Ray Young for superb audiovisual support at the meeting and for preparing many, and processing all, of the images and figures in this volume. The meeting would not have happened without the ceaseless effort, dedication, and logistical skill of Frank Cooper MBE, who maintained his flawless courtesy and good humour despite often extraordinary challenges in the best tradition of the Royal Navy. We would like to thank the following organizations for their generous support for the meeting. Without their generosity, this event could not have taken place: the Medical Research

Council, the Wellcome Trust, Wyeth Europa Ltd, Novartis Vaccines and Diagnostics, Inc., Dupont, University College London and University of Wisconsin. The following provided additional support for the participation of Papua New Guineans at the meeting: Michael Alpers, Ross Anderson, Stewart Gray Anderson, Richard Benfante, Gloria Chalmers, John Collinge, Cyril Curtain, Helen Fenbury, Skip Jackson, Deborah Lehmann, Shirley Lindenbaum, John and Coralie Mathews, Cedric Raine, Barbara Sherwood, Donald Simpson, Werner Sto¨ cklin, Margaret Spencer, Phillip Tarr, Gunilla Westermark, Per Westermark, Jerome Whitfield and Jettie Zigas. John Collinge1,* Michael P. Alpers1,2 1MRC Prion Unit, The National Hospital for Neurology and Neurosurgery, Institute of Neurology, Queen Square, University College London, London WC1N 3BG, UK E-mail address: jc@prion.ucl.ac.uk 2Centre for International Health, ABCRC, Curtin University, Health Research Campus, Shenton Park, GPO Box U1987, Perth, WA 9845, Australia *Author for correspondence. REFERENCES Alpers, M. P. In press a. The epidemiology of kuru: monitoring the epidemic from its peak to the end. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0071) Alpers, M. P. In press b. Some tributes to research colleagues and other contributors to our knowledge about kuru. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0098) Anderson, W. H. In press. Early perceptions of an epidemic. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0082) Anua, A. In press. ‘My late husband Mr Anua was a hardworking man.’ Phil. Trans. R. Soc. B 363. (doi:10.1098/ rstb.2008.0098) Asher, D. M. In press. Kuru: memories of the NIH years. Phil. Trans. R. Soc. B. 363. (doi:10.1098/rstb.2008.0098) Bavasa, A. In press. ‘My adopted daughter and then my second wife died of kuru.’ Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0098) Beasley, A. In press. Richard Hornabrook’s first impressions of kuru and Okapa. Phil. Trans. R. Soc. B 363. (doi:10. 1098/rstb.2008.0098) Benfante, R. In press. Reminiscences of an aspiring graduate student in the 1970s who worked on kuru-related projects with Dr Gajdusek. Phil. Trans. R. Soc. B 363. (doi:10. 1098/rstb.2008.0098) Bennett, J. H. In press. Family and population studies by the Adelaide Kuru Team, 1957–1965. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0098) Boone, K. In press. An account of the last autopsy carried out on a kuru patient. Phil. Trans. R. Soc. B 363. (doi:10.1098/ rstb.2008.0098) Brandner, S. et al. In press. Central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0091) Cathala, F. In press. Why I joined the research laboratory of Prof. D. Carleton Gajdusek in 1968. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0098) Collinge, J. In press. Lessons of kuru research: background to recent studies with some personal reflections. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0121) Collinge, J., Whitfield, J., McKintosh, E., Frosh, A., Mead, S., Hill, A. F., Brandner, S., Thomas, D. & Alpers, M. P. In press. A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb. 2008.0068) Curtain, C. C. In press.We see what we are trained to see, or must we? Some personal lessons from a brush with kuru research. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb. 2008.0116) Farquhar, J. In press. The expanded Laboratory of Collaborative and Field Research. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0116) Gajdusek, D. C. In press a. Kuru and its contribution to medicine. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb. 2008.0070) Gajdusek, D. C. In press b. Early images of kuru and the people of Okapa. Phil. Trans. R. Soc. B 363. (doi:10.1098/ rstb.2008.0116) Gajdusek, D. C. & Zigas, V. 1957 Degenerative disease of the central nervous system in New Guinea. The endemic occurrence of ‘kuru’ in the native population. N. Engl. J. Med. 257, 9 4–978. Gajdusek, D. C., Gibbs Jr, C. J. & Alpers, M. P. 1966 Experimental transmission of a kuru-like syndrome to chimpanzees. Nature 209, 794–796. (doi:10.1038/209 794a0) Gajdusek, D. C., Gibbs Jr, C. J. & Alpers, M. P. 1967 Transmission and passage of experimental ‘kuru’ to chimpanzees. Science 155, 212–214. Gibbs Jr, C. J., Gajdusek, D. C., Asher, D. M., Alpers, M. P., Beck, E., Daniel, P. M. & Matthews, W. B. 1968 Creutzfeldt–Jakob disease (spongiform encephalopathy): transmission to the chimpanzee. Science 161, 388–389. (doi:10.1126/science.161.3839.388) Gomea, T. In press. ‘We had to climb mountains and cross fast-flowing rivers.’ Phil. Trans. R. Soc. B 363. (doi:10. 1098/rstb.2008.0116) Hadlow, W. J. In press. Kuru likened to scrapie: the story remembered. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb. 2008.0116) Kakulas, B. A. In press. Personal reflections on the neuropathology of kuru. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0116) Kivita, I. In press. ‘Today I am so happy to see friends I once worked with many years ago.’ Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0116) Klitzman, R. In press. Kuru fieldwork in 1981.and beyond. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0116) Lindenbaum, S. In press a. Understanding kuru: the contribution of anthropology and medicine. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0072) Lindenbaum, S. In press b. First impressions of the Fore. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0116) Mabage, K. In press. ‘The people in every village they visited were so often mourning the dead’. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0116) Mathews, C. In press. Family life at Okapa as a ‘missus bilong dokta bilong kuru’. Phil. Trans. R. Soc. B 363. (doi:10. 1098/rstb.2008.0099) Mathews, J. D. In press. The changing face of kuru: a personal perspective. Phil. Trans. R. Soc. B 363. (doi:10. 1098/rstb.2008.0085) McLean, C. A. In press. The neuropathology of kuru and variant Creutzfeldt–Jakob disease. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0086) Mead, S. et al. 2003 Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. Science 300, 640–643. (doi:10.1126/science.1083320) Mead, S. Whitfield, J., Poulter, M., Shah, P., Uphill, J. Beck, J., Alpers M., Poulte, M. & Collinge, J. In press.

Genetic susceptibility, evolution and the kurur epidemic. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb. 2008.0087) Ombeya, P. In press. ‘We were only allowed to perform an autopsy on those patients we had taken good care of.’ Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0099) Pako,W. H. In press. The work of the Kuru Field Unit, Kuru Research Project of the Papua New Guinea Institute of Medical Research and MRC Prion Unit. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0099) Pekiyeva, T. In press. ‘The children of those who died of kuru are today still alive.’ Phil. Trans. R. Soc. B 363. (doi:10. 1098/rstb.2008.0099) Poki, K. In press. ‘We agreed that they could conduct an autopsy on my brother.’ Phil. Trans. R. Soc. B 363. (doi:10. 1098/rstb.2008.0099) Prusiner, S. B. In press. Reflections on kuru. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0099) Puwa, A. In press. ‘Most people still believe that kuru is caused by sorcery.’ Phil. Trans. R. Soc. B 363. (doi:10. 1098/rstb.2008.0099) Reid, L. M. H. In press. Memories of kuru while at Okapa, Papua New Guinea in 1957. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0099) Saweri, A. In press. Reminiscences about kuru and the people of Okapa. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb. 2008.0099) Scragg, R. F. R. In press. Kuru memories from 1957. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0088) Scrimgeour, E. M. In press. Some recollections about kuru in a patient at Rabaul in 1978, and subsequent experiences with prion diseases. Phil. Trans. R. Soc. B 363. (doi:10. 1098/rstb.2008.0088) Simpson, D. A. In press. The Adelaide Kuru Team in 1957– 1959. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008. 0088) Sto¨ cklin, W. H. In press. My kuru adventure. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0088) Taguse, T. In press. ‘I was selected to be trained as an aid post orderly.’ Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb. 2008.0088) Tarr, P. I. In press. The late 1970s: a lull in the action on kuru. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008. 0088) Tasa, K. In press. ‘Collecting human samples was very hard owing to the fear of sorcery.’ Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0088) Wadsworth, J. D. F., Joiner, S., Linehan, J. M., Asante, E. A., Brandner, S. & Collinge, J. In press. The origin of the prion agent of kuru: molecular and biological strain typing. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0069) Westermark, P. & Westermark, G. T. In press. Reflections on amyloidosis in Papua New Guinea. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0073) Whitfield, J. I. In press.Work among the people of the Okapa area from 1996 to the present. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0088) Whitfield, J. T., Pako, W. H., Collinge, J. & Alpers, M. P. In press. Mortuary rites of the South Fore and kuru. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008.0074) Zu Rhein, G. M. In press. My ‘brush’ with kuru research. Phil. Trans. R. Soc. B 363. (doi:10.1098/rstb.2008. 0088)

http://journals.royalsociety.org/content/j104810238060l8w/fulltext.pdf


Title Kuru - fifty years later. Author(s) Liberski PP, Brown P Institution Laboratory of Electron Microscopy and Neuropathology, Department of Molecular Pathology and Neuropathology, Chair of Oncology, Medical University Lodz, 8/10 Czechos³owacka Street, 92-216 Lodz, Poland. Source Neurol Neurochir Pol 2007 November-December; 41(6):548-556. Abstract Kuru, the first human neurodegenerative disease classified as a transmissible spongiform encephalopathy, prion disease or, in the past, slow unconventional virus disease, was first reported to Western medicine in 1957 by D. Carleton Gajdusek and Vincent Zigas. Thus, this year marks the 50th anniversary of kuru discovery, highlighted by the symposium The end of kuru: 50 years of research into an extraordinary disease organized by John Collinge and Michael Alpers at the Royal Society, London, November 11-12, 2007. In this review, we summarize some data on the epidemiology, neuropathology and clinical picture of kuru. Language ENG Pub Type(s) JOURNAL ARTICLE

PubMed ID 18224577

http://www.unboundmedicine.com/medline/ebm/record/18224577/full_citation/Kuru___fifty_years_later_


Kuru prions and sporadic Creutzfeldt–Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice

Jonathan D. F. Wadsworth, Susan Joiner, Jacqueline M. Linehan, Melanie Desbruslais, Katie Fox, Sharon Cooper, Sabrina Cronier, Emmanuel A. Asante, Simon Mead, Sebastian Brandner, Andrew F. Hill*, and John Collinge†

Medical Research Council Prion Unit and Department of Neurodegenerative Disease, University College London Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, United Kingdom

Communicated by Charles Weissmann, The Scripps Research Institute, Jupiter, FL, January 10, 2008 (received for review October 10, 2007)

Kuru provides our principal experience of an epidemic human prion disease and primarily affected the Fore linguistic group of the Eastern Highlands of Papua New Guinea. Kuru was transmitted by the practice of consuming dead relatives as a mark of respect and mourning (transumption). To date, detailed information of the prion strain type propagated in kuru has been lacking. Here, we directly compare the transmission properties of kuru prions with sporadic, iatrogenic, and variant Creutzfeldt–Jakob disease (CJD) prions in Prnp-null transgenic mice expressing human prion protein and in wild-type mice. Molecular and neuropathological data from these transmissions show that kuru prions are distinct from variant CJD and have transmission properties equivalent to those of classical (sporadic) CJD prions. These findings are consistent with the hypothesis that kuru originated from chance consumption of an individual with sporadic CJD.

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Discussion

In the present study, we have compared the transmission properties of kuru prions with sporadic, iatrogenic, and variant CJD prions in transgenic mice expressing human PrP valine 129 and in wild-type mice. These data establish that kuru prions have transmission properties equivalent to those of classical CJD prions and are distinct from vCJD prions. In agreement with this finding, the molecular strain types of PrPSc seen in kuru brain correspond to those seen in classical CJD rather than the distinct PrPSc types seen in vCJD or inherited prion disease. These collective data establish that kuru and classical CJD prions have closely similar prion strain properties and are consistent with the hypothesis that kuru originated from chance consumption of an individual with sporadic CJD (43). Human prion diseases with distinct etiologies are associated with a range of clinical presentations that are now seen as clinicopathological syndromes rather than individual disease entities (4, 55, 56). The central clinical feature of kuru is progressive cerebellar ataxia, and, in sharp contrast to sporadic CJD, dementia is a late and less prominent feature. A prodrome and three clinical stages consisting of an ambulatory stage, a sedentary stage, and a tertiary stage have been described in ref. 20. In this regard, the natural history of kuru is more reminiscent of vCJD in which early symptoms of distal sensory disturbance, joint pains, and psychiatric and behavioral changes are common before forthright dementia (4, 23, 25, 28). Despite these similarities in early clinical presentation, the molecular and neuropathological features of kuru are distinct from vCJD. In contrast to the occurrence of abundant florid PrP plaques that are the neuropathological changes seen in kuru lie within the spectrum of those seen in sporadic CJD. Unicentric PrP plaques, however, are unusually prominent and widespread (58, 59). This pattern of neuropathology most closely resembles a relatively rare subtype of sporadic CJD associated with long clinical duration and PRNP codon 129 heterozygosity in which kuru-type PrP plaques are also observed (10, 11, 46). Although PrP plaques are not a prominent feature of the most common subtypes of sporadic CJD, where diffuse synaptic PrP deposition predominates (10, 11, 46, 60), kuru-type plaques are a notable feature of iatrogenic CJD resulting from peripheral inoculation, most conspicuously after cadaveric pituitaryderived hormone exposure (61). This form of iatrogenic CJD also typically presents with a progressive cerebellar syndrome reminiscent of kuru, whereas cases of iatrogenic CJD arising from intracerebral or ocular inoculation usually manifest clinically as sporadic CJD, with a rapidly progressive dementia (62–65). These observations suggest that cerebellar onset and subsequent neuropathological changes may be determined in part by a peripheral route of exposure. The similarity of prion strain type in kuru and sporadic CJD demonstrated here now clearly suggests that peripheral routes of infection (predominantly dietary), rather than prion strain type, may be an important determinant of the clinicopathological phenotype of kuru. In this regard, the etiology of sporadic CJD remains unclear, although its remarkably uniform worldwide incidence and apparently random distribution suggest involvement of a stochastic process such as somatic PRNP mutation (2, 48, 66, 67). It is thus possible that part of the phenotypic and neuropathological heterogeneity seen in sporadic CJD could be related to peripheral versus central initiation of prion replication. Aside from route of exposure, additional factors may also influence the neuropathology and clinical features of kuru. A number of genetic modifiers of prion disease have been mapped in mice (16, 17). Although the genes responsible for mouse incubation time quantitative trait loci have not yet been identified, orthologous human genes are likely to be globally polymorphic with significant differences within and between Europe and the Fore. Furthermore, age is an important dete minant of youth may be associated with an atypical sporadic CJD neuropathology (70). The marked difference in mean age of kuru and sporadic CJD patients might thus account for some of the neuropathological differences that distinguish kuru from the majority of sporadic CJD cases. Our finding that kuru prions and vCJD prions have very different transmission properties supports previous molecular (9, 45–47, 49, 50), neuropathological (25, 57, 58), and transmission (14, 15, 26, 27) data indicating that vCJD is a highly distinct human prion strain. The pathogenesis of vCJD differs significantly from that of other forms of human prion disease. PrPSc is readily detectable in lymphoreticular tissues in vCJD and not in classical CJD or inherited prion disease (29, 32, 47, 71–76). Because kuru, iatrogenic CJD, and vCJD are caused by a peripheral route of exposure to infectious prions, it is possible that extensive lymphoreticular pathogenesis may result from this common route of exposure. However, the fact that tonsillar prion infection has not been detected in iatrogenic CJD associated with use of human cadaveric derived pituitary hormone (72, 75) or kuru (unpublished data) suggests that the distinct peripheral pathogenesis of vCJD is determined by prion strain type alone rather than route of infection. Although distinct from the vCJD prion strain, kuru is critically important as our only precedent of an orally acquired human prion disease epidemic. There remain striking parallels between the two outbreaks in terms of their clinical features, restricted temporal and geographic distribution, and the long and variable incubation times observed. Profound disease susceptibility is conferred by PRNP codon 129 in both diseases (4, 5, 15, 22). Because mouse models of prion disease demonstrate the importance of a small number of non-Prnp genetic factors in control of incubation time, it will be important to understand how the orthologous human genes modify susceptibility or incubation to both kuru and vCJD. ...snip...end...tss

Fig. 2. Molecular strain typing of human prion transmissions to mice. Immunoblots of proteinase K-digested brain homogenates from wild-type mice, human patients, or transgenic mice analyzed by enhanced chemiluminescence with ant i-PrP monoclonal antibodies ICSM35 (A) or 3F4 (B–D) are shown. The provenance of each brain sample is designated above each lane, and the type of human PrPSc detected in each sample (B–D) is designated below. (A) Transmission of vCJD prions (I344) and sporadic CJD prions (I764) to FVB/NHsd mice. (B) Transmission of vCJD prions (I348) to 129VV Tg152 mice. (C) Transmission of sporadic CJD prions with type 3 PrPSc (I4855) and kuru prions with type 3 PrPSc (I516) to 129VV Tg152 mice. (D) Transmission of kuru prions with type 2 PrPSc (I518) to 129VV Tg152 mice revealing a change in molecular strain type.

Fig. 3. Neuropathological analysis of transgenic mouse brain. Equivalent patterns of neuropathology are seen in 129VV Tg152 mice that propagate type 3 PrPSc after primary transmission of kuru prions or sporadic CJD prions that are distinct from 129VV Tg152 mice that propagate type 5 PrPSc after primary transmission of vCJD prions. Sketches represent the regional distribution of abnormal PrP deposition in transgenic mouse brain: diffuse synaptic PrP deposition (bars) and PrP plaques (circles). The bottom images show PrP immunohistochemistry with ICSM 35 (from the areas delineated by the blue boxes in the sketches) demonstrating nonflorid PrP plaques in the corpus callosum and diffuse synaptic PrP deposition in the thalamus. (Scale bar, bottom images: 100 m.)

Wadsworth et al. PNAS March 11, 2008 vol. 105 no. 10 3887

Materials and Methods

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www.pnas.orgcgidoi10.1073pnas.0800190105 Wadsworth et al. http://www.pnas.org/cgi/reprint/0800190105v1.pdf


Kuru in the 21st century—an acquired human prion disease

Thu Jun 22, 2006 19:44 70.110.82.186

The Lancet 2006; 367:2068-2074

DOI:10.1016/S0140-6736(06)68930-7

Kuru in the 21st century—an acquired human prion disease with very long incubation periods

John Collinge a , Jerome Whitfield a b, Edward McKintosh a, John Beck a, Simon Mead a, Dafydd J Thomas a and Michael P Alpers a c

Summary Background Kuru provides the principal experience of epidemic human prion disease. Its incidence has steadily fallen after the abrupt cessation of its route of transmission (endocannibalism) in Papua New Guinea in the 1950s. The onset of variant Creutzfeldt-Jakob disease (vCJD), and the unknown prevalence of infection after the extensive dietary exposure to bovine spongiform encephalopathy (BSE) prions in the UK, has led to renewed interest in kuru. We investigated possible incubation periods, pathogenesis, and genetic susceptibility factors in kuru patients in Papua New Guinea.

Methods We strengthened active kuru surveillance in 1996 with an expanded field team to investigate all suspected patients. Detailed histories of residence and exposure to mortuary feasts were obtained together with serial neurological examination, if possible.

Findings We identified 11 patients with kuru from July, 1996, to June, 2004, all living in the South Fore. All patients were born before the cessation of cannibalism in the late 1950s. The minimum estimated incubation periods ranged from 34 to 41 years. However, likely incubation periods in men ranged from 39 to 56 years and could have been up to 7 years longer. PRNP analysis showed that most patients with kuru were heterozygous at polymorphic codon 129, a genotype associated with extended incubation periods and resistance to prion disease.

Interpretation Incubation periods of infection with human prions can exceed 50 years. In human infection with BSE prions, species-barrier effects, which are characteristic of cross-species transmission, would be expected to further increase the mean and range of incubation periods, compared with recycling of prions within species. These data should inform attempts to model variant CJD epidemiology.

Affiliations

a. MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, London WC1N 3BG, UK b. Papua New Guinea Institute of Medical Research, Goroka, EHP, Papua New Guinea c. Centre for International Health, Curtin University, Perth, Australia

Correspondence to: Prof John Collinge

http://www.thelancet.com/journals/lancet/article/PIIS0140673606689307/abstract


TSS

Listen to The Lancet This week's audio summary discusses an Article entitled "Kuru in the 21st century - an acquired human prion disease with very long incubation periods". Also covered is a Lecture assessing climate change and its impact on health, and an Editorial about the roll-out of cervical cancer vaccines worldwide. >>

http://www.thelancet.com/webfiles/images/clusters/thelancet/audio/24June2006.mp3


further into this study;


Discussion

The early clinical, epidemiological, and anthropological study of kuru; the recognition of its neuropathological, and then causal parallels to ovine scrapie;20 and then crucially, the experimental transmission of the disease

to primates,21 originated the concept of the human transmissible spongiform encephalopathies, which was followed in turn by the eventual unifying concept of the mammalian prion diseases. However, in addition to the central historical importance of kuru, study of the end-stage of this epidemic offers a unique opportunity to study the variables of a near-complete epidemic of human prion disease. In particular, recognition of the incubation periods possible after natural prion infection in people is important in providing an insight (from actual case histories rather than from mathematical models) into the probable span of the vCJD epidemic in the UK. Although estimation of kuru incubation periods early in the epidemic was difficult, and the timing of the actual infecting event for an individual can rarely be determined, the abrupt and permanent interruption of the source of infection, endocannibalism, in the late 1950s, has progressively allowed recognition of an enormous span of possible incubation periods, at its shortest extreme bracketed by the rare onset of disease in children as young as 5 years and extending up to (and perhaps beyond) the incubations covering more than half a century, as we describe here.In our field studies, we have interviewed many individuals who participated in traditional mortuary feasting or who described the participation of family members from the preceding generation. These detailed descriptions will be published elsewhere but have reaffirmed the oral histories of endocannibalism in the Fore recorded previously12,22–24 and that this practice ceased abruptly at the time of Australian administrative control over the kuru areas. Although isolated events might have occurred for a few years after this prohibition, we are confident that new exposures of individuals to kuru at mortuary feasts would not have occurred after 1960. Not only have no cases of kuru been recorded in people born after 1959 (and only nine were recorded in those born after 1956); but also all the 11 last recorded cases of kuru that we report here were born before 1950. If any source of infection remained, whether from surreptitious cannibalism, possible ground contam-ination with human prions at sites where food was prepared, or other lateral routes, we would expect individuals born after this period to have kuru—especially since children are thought to have had shorter incubation periods than adults. However, no such cases have been observed. Additionally, although a fraction of hamster-adapted scrapie prions have been shown to survive in soil for at least 3 years,25 the mortuary feast practices (during which the entire body would be consumed) were undertaken so that any substantial contamination of soil would not have occurred, and traditional bamboo knives and leaf plates were burned after the feast. Furthermore, no clusters of kuru cases, as seen earlier in the epidemic,26 have been recorded for many years. We have also reviewed the assertion that maternal transmission of kuru did not occur, and saw no evidence for maternal transmission from kuru archives, interviews of colleagues who have practised medicine in the Fore, or local oral history. Again, any possible vertical route of kuru transmission would have resulted in the presence of kuru in children born after 1960, especially since kuru was common in women of childbearing age; no such cases have occurred.With respect to extrapolation of incubation periods of BSE prion infection in people, we should recognise that the kuru epidemic arose from intraspecies recycling of infectious prions. However, transmission of prions between different mammalian species is associated with a species barrier, which is better described as a transmission barrier, because of the importance of within-species prion strain type, in addition to species-specific differences in its determination.27 The biological effects of such a barrier are: extended mean incubation period; increased spread of incubation periods in individual animals; and reduced attack rate (in which only a fraction of inocu ated animals will succumb), by comparison with the 100% mortality generally associated with within-species inoculation with high-titre infectivity. Incubation periods approaching the natural lifespan of the inoculated species are often seen in such primary cross-species transmissions of prions. Second and subsequent passage of prions within the new species is always associated with adaptation involving a considerable shortening of the mean and spread of incubation periods and high or total lethality to high-titre inocula. Thus, estimation of the range of possible incubation periods in human BSE infection needs superimposition of the effect of a transmission barrier onto these findings of natural human incubation periods. The mean incubation period for kuru has been estimated to be around 12 years,27 with a similar estimate in iatrogenic CJD associated with the use of human-cadaver-derived pituitary growth hormone.28 As shown here, maximum incubation periods in kuru can exceed 50 years. The transmission barrier of BSE between cattle and human beings is unknown and cannot be directly measured. However, the cattle-to-mouse barrier for BSE has been well characterised experimentally by comparative endpoint titration. BSE prions transmit readily to laboratory mice, including after oral dosing.29 The murine LD50 (lethal dose causing 50% mortality) in C57Bl/6 mice is about 500-fold higher than that in cattle;30 this barrier also results in a three-fold to four-fold increase in mean incubation period.27 Mean incubation periods of human BSE infection of 30 years or more should therefore be regarded as possible, if not probable,27 with the longest incubation periods approaching (and perhaps exceeding) the typical human lifespan. The shortest incubation periods in kuru were estimated from the age of the youngest patients—suggesting that the shortest incubation period was Articles www.thelancet.com Vol 367 June 24, 2006 2073 4–5 years. Similarly in vCJD, although the total clinical caseload so far has been small, the youngest onsets of vCJD have been at age 12 years or above, providing an early estimate of a minimum incubation period. Furthermore, prion disease in mice follows a well-defined course with a highly distinctive and repeatable incubation time for a specific prion strain in a defined inbred mouse line. In addition to the PrP gene, a few additional genetic loci with a major effect on incubation period have been mapped.4,31,32 Human homologues of such loci could be important in human susceptibility to prion disease, both after accidental human prion exposure and after exposure to the BSE agent. By definition, patients identified so far with vCJD are those with the shortest incubation periods for BSE. These patients could have received an especially high dose of BSE prions. However, no unusual history of dietary, occupational, or other exposure to BSE has been reported from case-control studies. Because of the powerful genetic effects on incubation period in laboratory animals, vCJD patients identified could represent a distinct genetic subpopulation with unusually short incubation periods to BSE prions, with vCJD so far occurring predominantly in those individuals with short incubation time alleles at these multiple genetic loci, in addition to having the homozygous PRNP genotype of codon 129 methionine. Therefore, a human BSE epidemic may be multiphasic, and recent estimates of the size of the vCJD epidemic based on uniform genetic susceptibility could be substantial underestimations.33,34 Genes implicated in species-barrier effects, which would further increase both the mean and range of human BSE incubation periods, are also probably relevant. In this context, a human epidemic will be difficult to accurately model until such modifier loci are identified and their gene frequencies in the population can be measured.4Heterozygosity at PRNP codon 129 is a major determinant of susceptibility to and incubation time of human prion diseases.5,7,9,35 As expected, most of these recent kuru cases with extended incubation periods (ei ht of ten) were heterozygotes. We have reported previously that most elderly survivors of exposure to traditional mortuary feasts are heterozygous.9 Although the study included a small number of patients with kuru with long incubation periods, we saw no evidence of association with PRNP haplotype,10 HLA-DQ7,18 APOE,36 or PRND alleles.13

Contributors

J Whitfield led the field patrol team throughout the study and investigated all suspect cases; E McKintosh provided assistance during this time. J Beck and S Mead undertook the molecular genetic studies. J Collinge, M P Alpers, E McKintosh, and D J Thomas did field neurological examinations. J Collinge and M P Alpers supervised the study and drafted the manuscript. All authors contributed to and approved the final version of the manuscript. .........

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http://www.thelancet.com/journals/lancet/article/PIIS0140673606689307/abstract


Prion infections, blood and transfusions

Adriano Aguzzi* and Markus Glatzel

Prion infections lead to invariably fatal diseases of the CNS, including

Creutzfeldt–Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE), and scrapie in sheep. There have been hundreds of instances in which prions have been transmitted iatrogenically among humans, usually through neurosurgical procedures or administration of pituitary tissue extracts. Prions have not generally been regarded as bloodborne infectious agents, and case–control studies have failed to identify CJD in transfusion recipients. Previous understanding was, however, questioned by reports of prion infections in three recipients of blood donated by individuals who subsequently developed variant CJD. On reflection, hematogenic prion transmission does not come as a surprise, as involvement of extracerebral compartments such as lymphoid organs and skeletal muscle is common in most prion infections, and prions have been recovered from the blood of rodents and sheep. Novel diagnostic strategies, which might include the use of surrogate markers of prion infection, along with prion removal strategies, might help to control the risk of iatrogenic prion spread through blood transfusions. ...

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INTRODUCTION

Prion diseases, also termed transmissible SPONGIFORM ENCEPHALOPATHIES, constitute a group of neurodegenerative conditions that are transmissible within and between mammalian species. A characteristic of these diseases is the accumulation of a misfolded prion protein, PrPSc, which is a post-translationally modified form of the host-encoded prion protein (PrPC). The processes underlying PrPSc formation remain enigmatic, but there is little doubt that a conformer of PrPC, which might exist in an oligomeric form,1 is identical to the infectious entity.2 Prions damage the brain by transmitting toxic signals to cells expressing PrPC.3 Although genetic evidence has been taken to indicate that human prion diseases have been with us since prehistoric times,4 the first documented cases of Creutzfeldt–Jakob disease (CJD) date back only 85 years.5–7 Since then, it has become obvious that human prion diseases have three distinct etiologies: they can arise in the absence of any documented exposure to infectious prions as sporadic CJD (sCJD), as an autosomal dominantly inherited disease in the case of genetic, or familial, CJD (gCJD/fCJD), or as an acquired condition in the case of IATROGENIC and variant CJD (iCJD, vCJD), or kuru, which resulted from cannibalism.8

Some prion diseases that occur in animals might have been recognized several centuries ago, as suggested by early descriptions of sheep diseases that seem to correspond to scrapie. Most prion diseases affecting animals, however, were discovered relatively recently.6 A transmissible spongiform encephalopathy affecting cattle (bovine spongiform encephalopathy, or BSE) has caused a massive epidemic in European countries, affecting around 2 million animals.9 Epidemiological, biochemical, neuropathological and transmission studies have substantiated the concern that BSE prions might have crossed the species barrier between cattle and humans, resulting in a novel form of human prion disease, vCJD.10–13 During 1996–2001, the incidence of vCJD in the UK rose year upon year, evoking fears of a large upcoming epidemic.

Since 2001, however, the incidence of vCJD in the UK appears to have been stabilizing, indicating that the extent of the epidemic might be limited.14 As might be expected for in frequent stochastic events, the numbers of new cases of vCJD fluctuate from year to year. For example, data available on the web page of the National CJD Surveillance Unit15 show that the number of onsets of vCJD was higher in 2004 than it was in 2003, but this is not necessarily indicative of an upward trend. It must be assumed that a number of asymptomatic carriers of vCJD exist in human populations that have been exposed to BSE. The existence of such a chronic carrier state is a logical and unavoidable consequence of the long incubation time of prion diseases, which is typically in the order of several years and—in the case of oral exposure to prions—can reach several decades. Consequently, anybody who has contracted the infection but has not developed clinical signs and symptoms might be consider ed a carrier. Some of these carriers are likely be ‘preclinical’, and will proceed, in due course, to the development of disease.

Alternatively, it is conceivable that the carrier state can persist for an indefinite period of time, in which case infected individuals could be regarded as ‘permanent asymptomatic (sub clinical) carriers’. Studies performed in rodents indicate that the permanent subclinical carrier state might be a common phenomenon, such as occurs when immune deficient mice are exposed to prions.16 Unlinked anonymous screens for hallmarks of prion infection in archival tissues have suggested that the prevalence of individuals with sub clinical vCJD might be higher than previously antici pated, and could reach 237 cases per million individuals.17

The recent discovery of transmission of vCJD via blood in three individuals indicates with near certainty that blood-borne prion transmission, in conjunction with an unknown prevalence of vCJD-infected carriers, leads to secondary transmission of host-adapted prions.18 Consequently, the vCJD epidemic might be prolonged, or, in the worst-case scenario, vCJD be rendered endemic and selfsustained. In this article, we review how prions could act as blood-borne infectious agents, and consider strategies aimed at minimizing the risk of secondary trans mission of prion diseases.

TRANSMISSION OF PRION DISEASES IN HUMANS

The cause of most human prion diseases is unknown. In the case of sCJD, the term ‘sporadic’ is used as a euphemism, meaning that we have no idea about the origin of this form of CJD. By contrast, gCJD always segregates within families with mutations in the gene encoding the prion protein (PRNP), suggesting that these mutations are causally involved in disease pathogenesis. As no families have been described in which gCJD segregates with mutations in genes other than PRNP, it has been difficult to use human genetics to understand the pathogenesis of prion diseases. The discovery of PRNP mutations in gCJD has led to the proposal that at least some cases of sCJD might be due to somatic PRNP mutations analogous to those found in the germline of gCJD patients. It is equally possible, however, that some of the cases of alleged sCJD derive from hitherto unrecognized infectious causes. In apparent agreement with the ‘intrinsic’ origin of sCJD, which accounts for more than 90% of all human prion diseases, epidemiological studies were not able to identify a conclusive link between this form of CJD and external risk factors.19 This fact is reflected in the pathological and biochemical features of these diseases. Although low levels of PrPSc and prion infectivity can be demonstrated in peripheral sites such as lymphoid organs or skeletal muscle,20,21 the highest levels of PrPSc and prion infectivity appear to occur in the CNS. These facts might account, at least in part, for the lack of evidence of sCJD transmission by labile or stable blood products.22 Indeed, several retrospective studies have failed to identify blood transfusion or exposure to plasma products as risk factors for the development of sCJD,19 and prion diseases appear to be exceedingly rare in hemophiliacs, a group of patients that is at particularly high risk of contracting emerging blood-borne infectious diseases. Although these studies cannot exclude the possibility that transmission of sCJD might have occurred through blood transfusions in rare cases, and despite the fact that the etiology of sCJD is unclear, it would appear that transmission of sCJD by trans fusion of blood or blood products does not play a major role in the pathogenesis of this disease entity.

In the case of acquired prion diseases, however, the situation is very different. For vCJD, high levels of prion infectivity and of PrPSc have been detected in lymphoid organs such as the appendix and tonsils (Figure 1).23,24 For this reason, it has been speculated for almost a decade that vCJD might be associated with a higher risk of blood-borne transmission than sCJD. It is important to be cautious, however, as the differences in the organ tropism of sCJD and vCJD might be quantitative rather than qualitative, and PrPSc has been detected in the lymphoid organs of both vCJD and sCJD patients.21 Initial studies have failed to detect PrPSc and prion infectivity in the blood of patients with vCJD, but these negative data are likely to be attributable to the lack of sensitivity of the assays available at the time.23

The recent identification of three individuals with probable transmission of vCJD via blood transfusion has provided tragic evidence that vCJD prions can indeed be transmitted through blood (Figure 2). On the basis of the epi demiological and pathogenetic considerations discussed above, it can only be a matter of time before further cases of blood-transfusion-associated cases of vCJD will ensue (Figure 3). In the first of the cases reported, a patient received a single unit of non-leukodepleted erythrocyte concentrate from an individual who went on to develop vCJD 3.5 years later, and was therefore likely to have been subclinically prion-infected at the time of the donation. The recipient developed vCJD 6.5 years following the transfusion.25

In the second case, transmission of prion disease occurred again via a single unit of nonleukodepleted red-blood-cell concentrate. The donor developed vCJD 2 years following blood donation, again raising the possibility of pre clinical infection at the time of the donation. 18 The recipient died of causes unrelated to the prion infection 5 years after the transfusion. Although this individual did not display overt signs of vCJD, PrPSc could be detected in lymphoid organs, enforcing the concept of subclinical prion disease in this individual. Recently, a third case of blood-borne prion transmission has been reported.26 In this case, the incubation time in the recipient was 8 years, whereas the donor showed vCJD symptoms 20 months following his blood donation. Until now, sequencing of the PRNP gene in all individuals who succumbed to vCJD revealed homozygosity for the sequence ‘ATG’, which encodes methionine, at codon 129. In the general population, only 33% of people are homozygous for ATG at this codon of PRNP, so this particular genetic trait, known as the MM genotype, has been regarded as a risk factor for vCJD.8 The second identified recipient of prioninfected blood, however, was heterozygous for methionine/valine at codon 129 (MV genotype).

The MV genotype is underrepresented in sporadic and acquired CJD, and has therefore been considered a protective genetic trait. The fact that this individual died of a cause unrelated to prion disease raises the question of whether MV heterozygotes might develop a permanent carrier status, in which the prion replicates within their body but clinical signs are absent for an indeterminate period of time. Of course, it would be imprudent to draw far-reaching conclusions on the basis of three cases of blood-borne prion infection. We deem it justified, however, to highlight a number of surprising details that have become clear on analysis of these cases.

First, vCJD prions can indeed propagate using blood as a vector. In the past, this idea has often been regarded as ‘worst-case scenario’, ‘highly speculative’, and ‘barely a theoretical possibility’. The wishful thinking of many physicians involved in blood transfusion has often conjured up a sense of safety, which, as we regrettably now know, is unwarranted.

Second, a single unit of vCJD-prion-infected blood is sufficient to cause transmission of the disease. This fact is particularly unsettling, as it can only be taken to signify that the concentration of ID50 units in blood is relatively high. One ID50 unit is defined as the infectious dose sufficient to establish infection in 50% of recipients; animal experiments indicate that the amount of prion infectivity needed to reach one ID50 unit is much higher when prions are administered intravenously than when they are inoculated intracerebrally.

Third, blood from preclinically vCJD-infected patients can be infectious. Although not unexpected, this aspect is particularly worrisome, as it suggests that preclinical donors might subjectively not consider themselves at risk. Consequently, the only way to identify such donors would be to subject the donation to a prion screen of satisfactory sensitivity, which is currently unavailable.

Last, despite all epidemiological evidence to the contrary, patients who are methionine/valine heterozygous at codon 129 of the PRNP gene are susceptible to infection with vCJD prions, which raises several important questions. Is the virulence of BSE prions enhanced when passaged from human to human, as opposed to the original bovine to human situation? Passaging experiments of scrapie infectivity between mice and hamsters indicate that this scenario is highly plausible.6 Even more importantly, can vCJD infection of heterozygous individuals establish a permanent subclinical carrier state? Although this situation might constitute a best-case scenario for the infected individuals, it could be disastrous from an epidemiological viewpoint, as it might lead to an unrecognized and possibly self-sustaining epidemic. ...

snip... full text ;

JUNE 2006 VOL 2 NO 6 AGUZZI AND GLATZEL NATURE CLINICAL PRACTICE NEUROLOGY 329

www.nature.com/clinicalpractice/neuro


see full blog ;

http://blogs.nature.com/news/blog/2006/06/cjdrelated_disease_can_incubat.html



Thursday, July 24, 2008

Prion diseases are efficiently transmitted by blood transfusion in sheep

Submitted April 18, 2008 Accepted June 28, 2008

http://vcjdblood.blogspot.com/2008/07/prion-diseases-are-efficiently.html



Saturday, December 08, 2007

Transfusion Transmission of Human Prion Diseases

http://vcjdblood.blogspot.com/2006/12/vcjd-case-study-highlights-blood.html



Saturday, January 20, 2007
Fourth case of transfusion-associated vCJD infection in the United Kingdom

http://vcjdtransfusion.blogspot.com/2007/01/fourth-case-of-transfusion-associated.html



CHRONIC WASTING DISEASE CWD

http://chronic-wasting-disease.blogspot.com/



Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA

http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html



NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 2007

http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html


http://nor-98.blogspot.com/



SCRAPIE USA

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



TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TME

http://transmissible-mink-encephalopathy.blogspot.com/



TSE advisory committee for the meeting December 15, 2006


From: Terry S. Singeltary Sr.

To: FREAS@CBER.FDA.GOV

Cc: william.freas@fda.hhs.gov ; rosanna.harvey@fda.hhs.gov

Sent: Friday, December 01, 2006 2:59 PM

Subject: Re: TSE advisory committee for the meeting December 15, 2006 [TSS SUBMISSION]

http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f3413&disposition=attachment&contentType=msw8



FDA FAILED US

http://fdafailedus.blogspot.com/



SCIENCE BUSHWHACKED

http://sciencebushwhacked.blogspot.com/



Sunday, July 20, 2008 Red Cross told to fix blood collection or face charges 15 years after warnings issued, few changes made to ensure safety

http://vcjdblood.blogspot.com/2008/07/red-cross-told-to-fix-blood-collection.html



10 people killed by new CJD-like disease


Public release date: 9-Jul-2008

Since Gambetti's team wrote a paper describing an initial 11 cases referred to his centre between 2002 and 2006 (Annals of Neurology, vol 63, p 697),
another five have come to light. "So it is possible that it could be just the tip of the iceberg," Gambetti says.

snip...end


http://www.eurekalert.org/pub_releases/2008-07/ns-tpk070908.php



sporadic CJD, the big lie

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



Thursday, July 10, 2008 A New Prionopathy update July 10, 2008

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html



MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE


http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html



Saturday, June 21, 2008 HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008


http://cjdmadcowbaseoct2007.blogspot.com/2008/06/human-and-animal-tse-classifications-ie.html


Tuesday, July 29, 2008
Heidenhain Variant Creutzfeldt Jakob Disease Case Report

http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html


1969

Infection as the Etiology of Spongiform Encephalopathy (Creutzfeldt-Jakob Disease)

Abstract. Fatal spongiform encephalopathy occurred in four chimpanzees 12 to 14 months after inoculation with suspensions of brain from four patients, respectively. Chimpanzee to chimpanzee transmission was effected without reduction in incubation period. Retransmission of the disease to a second chimpanzee occurred when an inoculum that had been stored at -70°C for over 2 years was used.


C. J. GIBBS, JR.
D. C. GAJDUSEK
National Institute of Nelurological
Diseases and Stroke,
Bethesda, Maryland 20014
References and Notes
1. C. J. Gibbs, Jr., D. C. Gajduisek, D. M.
Asher, M. P. Alpers, E. Beck, P. M. Daniel,
W. B. Matthews, Science 161, 388 (1968).
2. The brain biopsy from patient 1 and the
brain autopsy from patient 4 were obtained
through the courtesy of Dr. W. B.
Matthews of Derby, England, and Dr. Peter
Daniel and Mrs. Elisabeth Beck of Maudsley
Hospital, London, England; frozen brain tissue
from patient 2 was obtained from Dr. E.
R. Ross of the Chicago Wesley Memorial
Hospital and Northwestern University, Chicago,
Illinois; and frozen brain tissue from
patient 3 was obtained from Dr. Alfred Pope
of McLean Hospital, Boston, Massachusetts.
3. D. C. Gaidusek, C. J. Gibbs, Jr., M. Alpers,
Natuire 209, 794 (1966).
4. - Science 155, 212 (1967).
5. E. Beck, P. M. Daniel, W. B. Matthews, D.
L. Stevens, M. P. Alpers, D. M. Asher, D.
C. Gajdusek, C. J. Gibbs, Jr., Brain, in press.
6. P. W. Lampert, K. M. Earle, C. J. Gibbs,
Jr., D. C. Gajdusek, J. Neutropathol. Exp.
Neurol. 28, No. 3, 353 (1969).
7. D. C. Gajdusek, C. J. Gibbs, Jr., D. M.
Asher, E. David,, Science 162, 693 (1968).
15 May 1969; revised 15 July 1969



Experimental Subacute Spongiform Virus
Encephalopathies in Primates and Other Laboratory Animals

Abstract. The host range of subacute spongiform virus encephalopathies is
described. The asymptomatic incubation period and the duration of the illnesses
in various species of animal hosts is discussed along with information on addi-
-tional species of Old World and New World monkeys and the domestic cat, which
have been shown to be susceptible to subacute spongiform virus encephalopathies.


68

References and Notes

1. D. C. Gajdusek, C. J. Gibbs, Jr., M. Alpers,
Nature 209, 794 (1966).
2. C. J. Gibbs, Jr., Curr. Top. Microbiol. 40,
44 (1967); -- and D. C. Gajdusek, Amer.
J. Trop. Med. Hyg. 19, 138 (1970).
3. C. J. Gibbs, Jr., D. C. Gajdusek, D. M.
Asher, M. P. Alpers, E. Beck, P. M. Daniel,
W. B. Matthews, Science 161, 388 (1968);
G. J. Gibbs, Jr., and D. C. Gajdusek, ibid.
165, 1023 (1969).
4. D. C. Gajdusek, C. J. Gibbs, Jr., D. M.
Asher, E. David, ibid. 162, 693 (1968); D. C.
Gajdusek and C. J. Gibbs, Jr., Nature 230,
588 (1971); ibid. 240, 351 (1972).
5. C. J. Gibbs, Jr., and D. C. Gajdusek, Nature
236, 73 (1972).
6. R. F. Marsh, thesis, University of Wisconsin
( 1968); D. Burger, R. Eckroade,
0. M. ZuRhein, R. P. Hanson, J. Infec. Dis.
120, 713 (1969); R. J. Eckroade, G. M.
ZuRhein, R. F. Marsh, R. P. Hanson, Scienc-
e 169, 1088 (1970).
7. N. G. Rogers, M. Basnight, C. J. Gibbs, Jr.,
The induction or transfer of enzyme
activity would be an attractive mode
of therapy for some of the enzyme
deficiency diseases. Rugstad and his
co-workers (1) have shown that bilirubin
uridine diphosphate (UDP)
glucuronyltransferase (E.C. 24.1.17)
activity could be transferred into enzyme
deficient homozygous Gunn rats.
This was accomplished by subcutaneous
transplantation of a clonal strain of
rat hepatoma cells (2). However, transplantation
of a viable neoplastic tissue
Fig. 1. Sequential histological appearance
of the tissues after grafting. (a) Three
weeks after the graft procedure. The pale
graft is surrounded by fibrotic tissues
and some inflammatory cells. (b) Six
weeks after the graft procedure. The graft
seems to be near the periphery. Fibrotic
tissues cannot be seen. (c) Nine weeks
after grafting. The size of the tissues
has diminished. (d) Twelve weeks after
grafting. No visible graft tissue can be
identified. The location of the graft can
be identified by the cleft.
D. C. Gajdusek, Nature 216, 446 (1967);
D. C. Gajdusek, C. J. Gibbs, Jr., N. G.
Rogers, M. Basnight, J. Hooks, ibid. 235,
104 (1972).
8. E. J. Field, Lancet 1968-I, 981 (1968).
9. D. A. Peterson, L. G. Wolfe, F. Deinhart,
D. C. Gajdusek, C. J. Gibbs, Jr., Nature,
in press.
10. I. Zlotnik and J. C. Rennie, J. Comp. Pathol.
75, 147 (1965).
11. R. P. Hanson, R. J. Eckroade, R. F. Marsh,
G. M. ZuRhein, C. L. Kanitz, D. P. Gustafson,
Science 172, 859 (1971).
12. R. L. Chandler and B. A. Turfey, Res. Vet.
Sci. 13, 219 (1972).
13. W. J. Hadlow, personal communication
(1973).
14. R. M. Barlow, J. Clin. Pathol. 25, 102 (1972).
15. J. L. Hourrigan and A. L. Klingsporn, personal
communication (1973).
16. , H. A. McDaniel, M. N. Riemenschneider,
J. Amer. Vet. Med. Ass. 154, 538
(1969).
30 April 1973; revised 12 June 1973


5 OCTOBER 1973 SCIENCE, VOL. 182


Subject: Human Tissues for Transplantation, Recall Nationwide and Internationally (CJD TSE RISK, among other infectious diseases risk)
Date: July 25, 2006 at 10:21 am PST

RECALLS AND FIELD CORRECTIONS: BIOLOGICS -- CLASS I
______________________________
PRODUCT
Human Tissues for Transplantation, Recall # B-0431-6
a) Patellar Tendon of varying sizes;
b) Patellar Tricortical Wedge;
c) Precision Graft of varying sizes;
d) RESERVE Cortical-Cancellous Ring of varying sizes;
e) Saphenous Veins of varying sizes;
f) SELECT Fibula Wedge of varying sizes;
g) SR Coritcal Block of varying sizes;
h) Tangent - Impacted Cortical Wedge of varying sizes;
i) Tibialis Anterior Tendon;
j) Tibialis Posterior Tendon;
k)TLIF of varying sizes;
l) Tricortical Block 9mm;
m) Unicortical Blocks of varying sizes;
n) Achilles Tendon W/ Calcaneus L=>180mm;
o) ACSR Coritcal Block of varying sizes;
p) ASR Cortical-Cancellous Block;
q) Bicortical Block of varying sizes;
r) BioCleanse® Patellar Tendon Hemi of varying sizes;
s) BioCleanse® Patellar Tendon Preshaped of varying sizes;
t) BioCleanse® Patellar Tendon Whole;
u) BioCleanse® Tibialis Anterior Tendon >= 200mm;
v) Cancellous Chips of varying sizes;
w) Cancellous Cubes of varying sizes;
x) Cornerstone L-ASR of varying sizes;
y) Cortical Cancellous Chips of varying sizes;
z) Cortical Strip of varying sizes;
aa) Corticocancellous Chips 40/60 Blend (1-3mm) 90cc;
bb) Dowel, Unicortical 14mm;
cc) Femoral Head W/O Cartilage;
dd) Femoral Shaft of varying sizes;
ee) FEMUR DISTAL (Left);
ff) Fibula Shaft, 50mm-75mm (L);
gg) FROZEN Impacted Cortical Wedge 8 x 20mm;
hh) HTO Wedge of varying sizes;
ii) Humeral Shaft, 50mm-100mm (L);
jj) HUMERUS WHOLE (Left);
kk) Iliac Block, Tricortical of varying sizes;
ll) Ilium Strip Tricortical 28-45mm x >24mm x 9mm;
mm) L-ACSR Cortical Block of varying sizes;
nn) Lordotic ASR Cortical-Cancellous Block of varying sizes;
oo) Lordotic MASR Cortical-Cancellous Block of varying sizes;
pp) Lordotic SR Cortical Block of varying sizes;
qq) Machined Cortical Ring of varying sizes;
rr) MASR Cortical-Cancellous Block of varying sizes;
ss) MD-II Dowel (Threaded) of varying sizes;
tt) MD-IV Threaded Cortical Dowel of varying sizes;
uu) Right/Left pulmonary hemi-artery;
vv) Semitendinosus Tendon, 200mm;
ww) Strips Cortical 090-110mm(L) x 18-20mm (W);
xx) Tibia Shaft, 50mm-75mm (L);
yy) Patellar Tendon (hemi)(International);
zz) Patellar Tendon Preshaped of varying sizes
CODE
snip...

RECALLING FIRM/MANUFACTURER
Recalling Firm: Regeneration Technologies, Inc., Alachua, FL, by letters dated October 14 and October 26, 2005.
Responsible Firm: Biomedical Tissue Services, Ltd., Fort Lee, NJ. Firm initiated recall is ongoing.
REASON
Human tissues, recovered from donors without adequate donor eligibility, were distributed.
VOLUME OF PRODUCT IN COMMERCE
11,097 allografts
DISTRIBUTION
Nationwide and Internationally

______________________________
PRODUCT
Human Tissues for Transplantation, Recall # B-1091-6:
a) ASCR Cortical Block (10x14x11);
b) Assembled Cortical-Cancellous Block (07x14x11);
c) Bicortical Block (14 mm x 20 mm);
d) Cancellous Chips;
e) Cancellous Cubes of varying sizes;
f) Cortical Cancellous Chips 40/60 Mix (1-3 mm) 30 cc;
g) Dowel, Unicortical 14 mm;
h) Iliac Block, Tricortical (16 mm x 15 mm);
i) Ilium Strip Tricortical of varying sizes;
j) MD-II Dowel (Threaded) of varying sizes;
k) MD-IV Threaded Cortical Dowel of varying sizes;
l) Patellar Tricortical Wedge (20 mm(H) x 25 mm(L));
m) Precision Graft of varying sizes;
n) SELECT Fibula Wedge of varying sizes;
o) SR Cortical Block of varying size;
p) Tangent -- Impacted Cortical Wedge of varying sizes;
q) Unicortical Block of varying sizes;
r) Achilles Tendon Preshaped;
s) Achilles Tendon with Calcaneous;
t) Cancellous Block;
u) Femoral Head w/o Cartilage;
v) Femoral Shaft (166 mm -- 202 mm (L));
w) Fibula Shaft of varying sizes;
x) HTO Wedge of varying sizes;
y) Patellar Tendon (hemi) of varying sizes;
z) Patellar Tendon (Whole);
aa) Patellar Tendon Preshaped (International);
bb) Patellar Tendon Preshaped of varying sizes;
cc) Tibialis Anterior Tendon;
dd) Tibialis Posterior Tendon;
CODE
snip...

RECALLING FIRM/MANUFACTURER
Recalling Firm: Regeneration Technologies, Inc., Alachua, FL, by letters dated October 14 and October 26, 2005.
Responsible Firm: Biomedical Tissue Services, Ltd., Fort Lee, NJ. Firm initiated recall is ongoing.
REASON
Human tissues, recovered from donors without adequate donor eligibility, were distributed.
VOLUME OF PRODUCT IN COMMERCE
1,487 allografts
DISTRIBUTION
Nationwide and Internationally

______________________________
PRODUCT
Human Tissue for Transplantation Tissues, Recall # B-1108-6:
a) Achilles Tendon;
b) Cancellous Chips 30cc, 4-10mm;
c) Tibialis Tendon, Anterior;
d) Tibialis Tendon, Posterior;
e) Patella Tendon, Hemi;
f) Ground Cancellous;
CODE
a) T2005-061-002, T2005-053-001, T2005-053-002, T2005-069-002, T2005-046-003, T2005-068-001, T2005-044-001, T2005-044-002, T2005-010-001, T2005-063-001, T2005-039-002, T2005-043-001, T2005-045-003, T2005-045-004, T2005-049-003, T2005-049-004, T2005-055-001, T2005-022-002, T2005-075-001, T2005-048-001, T2005-048-002, T2005-038-002, T2005-023-002, T2005-022-001, T2005-063-002, T2005-023-001, T2005-040-002, T2005-040-001, T2005-072-001, T2005-074-002, T2005-013-001, T2005-054-001, T2005-100-001, T2005-034-002;

b) T2005-018-004, T2005-018-003, T2005-024-001, T2005-024-002, T2005-024-003, T2005-025-001, T2005-013-003;

c) T2005-046-007, T2005-044-006, T2005-043-002, T2005-043-003, T2005-041-006, T2005-040-006, T2005-048-005, T2005-045-006, T2005-048-006, T2005-047-007;

d) T2005-048-004, T2005-044-003, T2005-040-004, T2005-047-010, T2005-041-005, T2005-045-005, T2005-047-009, T2005-049-005, T2005-040-003;

e) GL2005-147-003;

f) T2005-018-002, T2005-027-001, T2005-027-002, T2005-027-003, T2005-027-004, T2005-018-006, T2005-018-007, T2005-026-001
RECALLING FIRM/MANUFACTURER
Recalling Firm: Tissue Management Solutions, LLC, Scottsdale, AZ, by telephone on October 5, 2005, and by letter dated October 28, 2005.
Manufacturer: Lost Mountain Tissue Bank, Kennesaw, GA. Firm initiated recall is complete.
Responsible Firm: Biomedical Tissue Services Ltd., Fort Lee, NJ
REASON
Human tissues, recovered from donors without adequate donor eligibility, were distributed.
VOLUME OF PRODUCT IN COMMERCE
69 tissues
DISTRIBUTION
CO, IL, AZ, CA, TX, NV, KA and WI


http://www.fda.gov/bbs/topics/enforce/2006/ENF00961.html



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


----- Original Message -----
From: Terry S. Singeltary Sr.
To: jgoodman@cber.fda.gov
Sent: Friday, September 01, 2006 2:49 PM
Subject: RE- FDA FORMS TASK FORCE ON HUMAN TISSUE SAFETY


FDA News
FOR IMMEDIATE RELEASE
P06-122
August 30, 2006
Media Inquiries:
Paul Richards, 301-827-6242
Consumer Inquiries:
888-INFO-FDA



FDA Forms Task Force on Human Tissue Safety


snip...


“The primary goal of the new task force is to identify whether any additional steps are needed to further protect the public health while assuring the availability of safe products,” said Jesse Goodman, MD, MPH, director of CBER. “The creation of this task force is part of the agency's overall plan to ensure that all human cells and tissues are as safe as possible.”

While the agency believes most firms involved in tissue manufacturing comply with the new regulations, FDA wants to explore where additional steps could help strengthen its approach to making sure firms follow required practices to prevent the transmission of communicable diseases. The agency continues to work diligently to identify and, where appropriate, take action against establishments and individuals that violate the rules. These actions may include both administrative and criminal proceedings.

“FDA is committed to rapidly identifying and stopping those establishments and individuals that risk endangering the public health by not complying with the regulations,” said Margaret O’K Glavin, Associate Commissioner of the Office of Regulatory Affairs. “We also will continue to work with professional and trade associations to support their ongoing efforts to assure quality oversight of manufacturing operations and product safety.”

“The creation of this task force underscores FDA’s recognition that compliance with the rules in place to ensure recipient safety is our highest priority,” Dr. Goodman said.

Within the next three months, the task force will develop an action plan, and where necessary, propose changes to existing policies, as well as generate a set of recommendations, identify what resources are needed to support these actions and report on how the agency can immediately implement its action plan.

####


http://www.fda.gov/bbs/topics/NEWS/2006/NEW01440.html


THANK YOU DR. GOODMAN !!!


I only hope that you (FDA et al) are serious? ACTIONS speak louder than words, and only monetary damages AND jail will make some companies comply. I donated my mothers brain for the research of human TSE, she died 12-14-97 from the Heidenhain Variant of Creutzfeldt Jakob Disease, and since, have regretted ever doing it due to the various controversies that have taken place since, with tissue donations. I know others that feel the same way. Either get it under control now, or risk having less and less donated tissue to work with in science and the medical donor programs. ...


Thank You,

I am sincerely,


Terry S. Singeltary Sr.

P.O. Box 42

Bacliff, Texas USA 77518


CJD WATCH MESSAGE BOARD


TSS
NIH BODY SNATCHERS AT IT AGAIN, SELLING TO HIGHEST BIDDERS
Wed Jun 14, 2006 09:07
70.110.89.178

Charged With Stealing Parts From Corpses
Parts Allegedly Removed Before Cremation

POSTED: 5:55 am CDT May 18, 2007

ROCHESTER, N.Y. -- Three funeral home directors and four former employees of a biomedical supply company secretly removed skin, bone and other body parts from dozens of corpses awaiting cremation at Rochester funeral homes, prosecutors said Thursday.

An indictment unsealed Thursday charges the seven with body stealing, unlawful dissection and other counts. The most serious charges carry maximum 20-year prison sentences.

"Put yourself in the position of one of the family members," said Monroe County District Attorney Michael Green. "What we've heard from them is that this is just absolutely devastating."

Four of those charged worked at a suburban Rochester branch of now-defunct Biomedical Tissue Services of Fort Lee, N.J.

Four other men, including the company's owner, former dentist Michael Mastromarino, were charged last year with removing bone and tissue from 1,077 bodies at funeral homes without the permission of families. All have pleaded not guilty.

Prosecutors said Mastromarino made millions of dollars by selling body parts to biomedical companies that supply material for common procedures, including dental implants and hip replacements.

In October, seven funeral home directors linked to the scheme pleaded guilty in New York City to undisclosed charges and agreed to cooperate with investigators. They included the director of a funeral home that took parts from the body of "Masterpiece Theatre" host Alistair Cooke, who died in 2004, defense attorneys say.

Biomedical Tissue Services operated its only satellite office in the Rochester suburb of Brighton and paid funeral homes a standard fee of around $1,000 to lawfully harvest body parts.

The indictment alleges that employees Darlene Deats, 46; Kevin Vickers, 53; Nicholas Sloyer, 34; and Kirssy Knapp, 29, removed bone and tissue from 36 corpses in 2005 without getting the proper consent.

Also charged were Jason Gano, 31, former funeral director of Thomas E. Burger Funeral Home in Hilton, Scott Batjer, 37, director of Profetta Funeral Chapel in Webster, and Serrell Gayton, 59, director of Serenity Hills Funeral Chapel in Rochester.

Five of the defendants pleaded not guilty Thursday and were released. Vickers, in England attending his brother's wedding, was ordered to appear next week, and an arrest warrant was issued for Knapp, who failed to show up in court.

Sloyer's attorney, Paul MacAulay, said he did not knowingly commit a crime.

"He had no reason to doubt that any of the bodies that they were involved in were being processed without a valid consent," MacAulay said.
Copyright 2007 by The Associated Press.


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