Prion diseases are efficiently transmitted by blood transfusion in sheep
Prion diseases are efficiently transmitted by blood transfusion in sheep
Fiona Houston*, Sandra McCutcheon, Wilfred Goldmann, Angela Chong, James Foster, Silvia Siso, Lorenzo Gonzalez, Martin Jeffrey, and Nora Hunter Division of Animal Production and Public Health, Faculty of Veterinary Medicine, University of Glasgow, Glasgow, United Kingdom Neuropathogenesis Division, Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom Veterinary Laboratories Agency, Lasswade Laboratory, Edinburgh, United Kingdom
* Corresponding author; email: firstname.lastname@example.org.
The emergence of variant Creutzfeld-Jakob disease (vCJD), following on from the bovine spongiform encephalopathy (BSE) epidemic, led to concerns about the potential risk of iatrogenic transmission of disease by blood transfusion and the introduction of costly control measures to protect blood supplies. We previously reported preliminary data demonstrating the transmission of BSE and natural scrapie by blood transfusion in sheep. The final results of this experiment, reported here, give unexpectedly high transmission rates by transfusion of 36% for BSE and 43% for scrapie. A proportion of BSE-infected tranfusion recipients (3/8) survived for up to 7 years without showing clinical signs of disease. The majority of transmissions resulted from blood collected from donors at >50% of the estimated incubation period. The high transmission rates and relatively short and consistent incubation periods in clinically positive recipients suggest that infectivity titres in blood were substantial and/or that blood transfusion is an efficient method of transmission. This experiment has established the value of using sheep as a model for studying transmission of vCJD by blood products in humans.
Greetings again Dr. Freas et al at FDA,
THIS was like closing the barn door after the mad cows got loose. not only the red cross, but the FDA has failed the public in protecting them from the TSE aka mad cow agent. TSE agent i.e. bse, base, cwd, scrapie, tme, and any sub strains thereof. we do not know if these strains will or have transmitted to humans as subclinical TSE or clinical disease, and we do not know if they have or will transmit second, third, forth passage via friendly fire i.e. multiple potential routes via medical, surgical, pharmaceutical etc.
Saturday, December 08, 2007
Transfusion Transmission of Human Prion Diseases
Recovered Plasma, Recall # B-1660-08
Florida’s Blood Centers, Inc., Orlando, FL, by electronic mail and facsimile on June 4, 2007. Firm initiated recall is complete.
Blood product, collected from a donor considered to be at increased risk for variant Creutzfeldt-Jakob Disease (vCJD), was distributed.
VOLUME OF PRODUCT IN COMMERCE
Austria and FL
END OF ENFORCEMENT REPORT FOR JULY 23, 2008
see many more blood recalls below ;
Tuesday, October 09, 2007 nvCJD TSE BLOOD UPDATE
Saturday, December 08, 2007 Transfusion Transmission of Human Prion Diseases
Saturday, January 20, 2007 Fourth case of transfusion-associated vCJD infection in the United Kingdom
vCJD case study highlights blood transfusion risk 9 Dec 2006 by Terry S. Singeltary Sr. THIS was like closing the barn door after the mad cows got loose. not only the red cross, but the FDA has failed the public in protecting them from the TSE aka mad cow agent. TSE agent ie bse, base, cwd, scrapie, tme, ... vCJD case study highlights blood transfusion risk -
FDA FAILED US
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
Infectivity of bovine materials used in medicinal products and the
importance of inoculation route
3.221 The risk from infectivity present in medicinal products was considered by the
Southwood Working Party. They noted that ‘the greatest risk . . . would be from the
parenteral injection of material derived from bovine brain or lymphoid tissue’.538
(As described previously, it was generally accepted that the oral route was
considerably less efficient than the parenteral route.539)
3.222 In reality, different routes exist within the parenteral category – intracerebral,
intraperitoneal, intramuscular, intravenous, intraspinal and subcutaneous.
Experiments in 1978 looking at several of these routes found the efficiency between
them to vary. Intracerebral and intraspinal were generally the most efficient,
followed by intravenous, intraperitoneal and then subcutaneous.540 The fact that
certain medicinal products could be injected directly into the body (most commonly
intramuscularly) meant that in theory they would pose a greater risk than beef
products in food.
3.223 Various cattle tissues were of relevance to medicinal products, including
insulin, heparin, surgical catgut sutures and serum. The consideration given to these
materials prior to March 1996 is addressed in vol. 7: Medicines and Cosmetics.
533 SEAC 22/5
534 Wells, G. (1998) Preliminary Observations on the Pathogenesis of Experimental Bovine Spongiform Encephalopathy (BSE):
An Update, Veterinary Record, 142, 103
535 Wells, G., Hawkins, S., Green, P., Spencer, Y., Dexter, I. and Dawson, D. (1999) Limited Detection of Sternal Bone Marrow
Infectivity in the Clinical Phase of Experimental Bovine Spongiform Encephalopathy (BSE), Veterinary Record, 144, 292–4
536 Scott, M.R., Will, R., Ironside, J., Nguyen, H.-O., Tremblay, P., DeArmond, S.J. and Prusiner, S.B. (1999) Compelling
Transgenetic Evidence for Transmission of Bovine Spongiform Encephalopathy Prions to Humans, Proceedings of the
National Academy of Sciences of the USA, 96, 15137–42
537 Scott, M.R., Safar, J., Telling, G., Nguyen, H.-O., Groth, D., Torchia, M., Kochler, R., Tremblay, P., Walther, D., Cohen, F.,
DeArmond, S. and Prusiner, S. (1997) Identification of a Prion Protein Epitope Modulating Transmission of Bovine Spongiform
Encephalopathy Prions to Transgenic Mice, Proceedings of the National Academy of Sciences of the United States of
America, 94, 14279–84
538 IBD1 tab 2 para. 5.3.3
539 Kimberlin, R. and Walker, C. (1989) Pathogenesis of Scrapie in Mice after Intragastric Infection, Virus Research, 12, 213–20;
Diringer, H., Beekes, M. and Oberdieck, U. (1994) The Nature of the Scrapie Agent: The Virus Theory, Annals of The New
York Academy of Science, 724, 246–58; Prusiner, S., Cochran, S. and Alpers, S. (1985) Transmission of Scrapie in Hamsters,
Journal of Infectious Diseases, 152, 971–8
540 Kimberlin, R.H. and Walker, C.A. (1978) Pathogenesis of Mouse Scrapie: Effect of Route of Inoculation on Infectivity Titres
and Dose-Response Curves, Journal of Comparative Pathology, 88, 39–47
From: TSS (216-119-138-163.ipset18.wt.net) Subject: RE--CJD&CHILDREN-- could the 'v' in vCJD simply mean vaccineCJD? Date: September 10, 2000 at 8:47 am PST
######### Bovine Spongiform Encephalopathy #########
(Not to forget about the potential for some BSE cases to come from vaccinations containing pituitary-derived SRMs.)
TWA LITTLE minute http://www.bseinquiry.gov.uk/files/yb/1988/06/10001001.pdf
COMMERCIAL IN CONFIDENCE
NOT FOR PUBLICATION
NON-LICENSED HUMAN TISSUE DEVICES WERE NOT COMMERCIALLY AVAILABLE
I was quite prepared to believe in unofficial pituitary hormones, also in the 1970's, whether as described by Dr. Little, or in other circumstances, for animal use. snip... The fact that there were jars of pituitaries (or extract) around on shelves is attested by the still potent 1943 pituitaries, described in Stockell Hartree et al. (J/RF/17/291) which had come from the lab. at Mill Hill. Having taken the trouble to collect them, they were not lightly thrown out...
more on the 1968 medicine act, they forgot to follow
Draft cover letter to product licence holders (considered by Human and Vet Medicines including deer)
(It was noted with concern that hormone extracts could be manufactured by a veterinary surgeon for administration to animals under his care without any Medicines Act Control.)
TWA LITTLE STATEMENT 331
Subject: Louping-ill vaccine documents from November 23rd, 1946 Date: Sat, 9 Sep 2000 17:44:57 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de
######### Bovine Spongiform Encephalopathy #########
THE VETERINARY RECORD 516 No 47. Vol. 58 November 23rd, 1946
NATIONAL VETERINARY MEDICAL ASSOCIATION OF GREAT BRITAIN AND IRELAND
ANNUAL CONGRESS, 1946
The annual Congress, 1946, was held at the Royal Veterinary College, Royal College Street, London, N.W.I. from September 22nd to September 27th.
[skip to scrapie vaccine issue...tss]
Papers Presented to Congress
The papers presented to this year's Congress had as their general theme the progressive work of the profession during the war years. Their appeal was clearly demonstrated by the large and remarkably uniform attendance in the Grand Hall of the Royal Veterinary College throughout the series; between 200 and 250 members were present and they showed a keen interest in every paper, which was reflected in the expression of some disappointment that the time available for discussion did not permit of the participation of more than a small proportion of would-be contributors.
In this issue we publish (below) the first to be read and discussed, that by Dr. W. S. Gordon, M.R.C.V.S., F.R.S.E., "Advances in Veterinary Research." Next week's issue will contain the paper on "Some Recent Advances in Veterinary Medicine and Surgery in Large-Animal Practice" by Mr. T. Norman Gold, M.R.C.V.S. In succeeding numbers of the Record will be reproduced, also with reports of discussions, that by Mr. W. L. Weipers, M.R.C.V.S., D.V.S.M., on the same subject as relating to small-animal practice, and the papers by Mr. J. N. Ritchie, B.SC., M.R.C.V.S., D.V.S.M., and Mr. H.W. Steele-Bodger, M.R.C.V.S., on "War-time Achievements of the British Home Veterinary Services."
The first scientific paper of Congress was read by Dr. W. S. Gordon, M.R.C.V.S., F.R.S.E. on Monday, September 23rd, 1946, when Professor J. Basil Buxton, M.A., F.R.C.V.S, D.V.H., Prinicipal of the Royal Veterinary College, presided.
Advances in Veterinary Research
W.S. GORDON, PH.D., M.R.C.V.S., F.R.S.E.
Agriculteral Research Council, Field Station, Compton, Berks.
Louping-ill, Tick-borne Fever and Scrapie
In 1930 Pool, Browniee & Wilson recorded that louping-ill was a transmissible disease. Greig et al, (1931) showed that the infective agent was a filter-passing virus with neurotropic characters and Browniee & Wilson (1932) that the essential pathology was that of an encephalomyelitis. Gordon, Browniee, Wilson & MacLeod (1932) and MacLeod & Gordon (1932) confirmed and extended this work. It was shown that on louping-ill farms the virus was present in the blood of many sheep which did not show clinical symptoms indicating involvement of the central nervous system and that for the perpetuation and spread of the disease these subclinical cases were probably of greater importance that the frank clinical cases because, in Nature, the disease was spread by the tick, lxodes ricinus L. More recently Wilson (1945, 1946) has described the cultivation of the virus in a chick embryo medium, the pathogenic properties of this culture virus and the preparation of louping-ill antiserum.
Between 1931 and 1934 I carried out experiments which resulted in the development of an effective vaccine for the prevention of louping-ill.* This vaccine has been in general use since 1935 and in his annual report to the Animal Diseases Research Association this year, Dr. Greig stated that about 227,000 doses of vaccine had been issued from Moredun alone.
Dr. Gordon illustrated this portion of his paper by means of graphs and diagrams projected by the epidiascope.
This investigation, however, did not begin and end with the study of louping-ill; it had, by good fortune, a more romantic turn and less fortunately a final dramtic twist which led almost to catastrope. After it had been established that a solid immunity to louping-ill could be induced in sheep, a group of immunized and a group of susceptible animals were placed together on the tick-infected pasture of a louping-ill farm. Each day all the animals were gathered and their temperatures were recorded. It was anticipated that febrile reactions with some fatalities would develop in the controls while the louping-ill immunes would remain normal. Contrary to expectation, however, every sheep, both immune and control, developed a febrile reaction. This unexpected result made neccessary further investigation which showed that the febrile reaction in the louping-ill immunes was due to a hitherto undescribed infective agent, a Rickettsia-like organism which could be observed in the cytoplasm of the grannular leucocytes, especially the neutrophil polymorphs (MacLeod (1932), Gordon, Browniee, Wilson & MacLeod. MacLeod & Gordon (1933). MacLeod (1936). MacLeod collected ticks over many widely separated parts of Scotland and all were found to harbour the infective agent of tick-borne fever, and it is probable that all sheep on tick-infested farms develop this disease, at least on the first occasion that they become infested with ticks. When the infection is passed in series through susceptible adult sheep it causes a sever, febrile reaction, dullness and loss of bodily condition but it rarely, if ever, proves fatal. It is clear, however, that it aggravates the harmful effects of a louping-ill infection and it is a serious additional complication to such infections as pyaemia and the anacrobic infections which beset lambs on the hill farms of Northern Britain.
Studying the epidemiology of louping-ill on hill farms it became obvious that the pyaemic condition of lambs described by M'Fadyean (1894) was very prevalent on tick infested farms Pyaemia is a crippling condition of lambs associated with tick-bite and is often confused with louping-ill. It is caused by infection with Staphylococcus aureus and affected animals may show abscess formation on the skin, in the joints, viscera, meninges and elsewhere in the body. It was thought that tick-borne fever might have ben a predisposing factor in this disease and unsuccessful attempts were made by Taylor, Holman & Gordon (1941) to reproduce the condition by infecting lambs subcutaneously with the staphylococcus and concurrently produceing infections with tickborne fever and louping-ill in the same lambs. Work on pyaemia was then continued by McDiarmid (1946a, 1946b, 1946c), who succeeded in reproducing a pyaemic disease in mice, guinea-pigs and lambs similar to the naturally occuring condition by intravenous inoculation of Staphylococcus aureus. He also found a bacteraemic form of the disease in which no gross pyaemic lesions were observed. The prevention or treatment of this condition presents a formidable problem. It is unlikely that staphylococcal ???oid will provide an effective immunity and even if penicillin proved to be a successful treatment, the difficulty of applying it in adequate and sustained dosage to young lambs on hill farms would be almost insurmountable.
From 1931 to 1934 field trials to test the immunizing value and harmlessness of the loup-ill vaccine were carried out on a gradually increasing scale. Many thousands of sheep were vaccinated and similar numbers, living under identical conditions were left as controls. The end result showed that an average mortability of about 9 percent in the controls was reduced to less than 1 percent in the vaccinated animals. While the efficiency of the vaccine was obvious after the second year of work, previous bitter experience had shown the wisdom of withholding a biological product from widespread use until it had been successfully produced in bulk, as opposed to small-scale experimental production and until it had been thoroughly tested for immunizing efficiency and freedom from harmful effects. It was thought that after four years testing this stage had been reached in 1935, and in the spring of that year the vaccine was issued for general use. It comprised a 10 percent saline suspension of brain, spinal cord and spleen tissues taken from sheep five days after infection with louping-ill virus by intracerebral inoculation. To this suspension 0-35 percent of formalin was added to inactivate the virus and its safety for use as a vaccine was checked by intracerbral inoculation of mice and sheep and by the inoculation of culture medium. Its protective power was proved by vaccination sheep and later subjecting them, along with controls, to a test dose of living virus.
Vaccine for issue had to be free from detectable, living virus and capable of protecting sheep against a test dose of virus applied subcutaneously. The 1935 vaccine conformed to these standards and was issued for inoculation in March as three separate batches labelled 1, 2, and 3. The tissues of 140 sheep were employed to make batch 1 of which 22,270 doses were used; 114 to make batch 2 of which 18,000 doses were used and 44 to make batch 3 of which 4,360 doses were used. All the sheep tissues incorporated in the vaccine were obtained from yearling sheep. During 1935 and 1936 the vaccine proved highly efficient in the prevention of loup-ill and no user observed an ill-effect in the inoculated animals. In September, 1937, two and a half years after vaccinating the sheep, two owners complained that scrapie, a disease which had not before been observed in the Blackface breed, was appearing in their stock of Blackface sheep and further that it was confined to animals vaccinated with louping-ill vaccine in 1935. At that stage it was difficult to conceive that the occurrence could be associated with the injection of the vaccine but in view of the implications, I visited most of the farms on which sheep had been vaccinated in 1935. It was at this point that the investigation reached its dramatic phase; I shall not forget the profound effect on my emotions when I visited these farms and was warmly welcomed because of the great benefits resulting from the application of louping-ill vaccine, wheras the chief purpose of my visit was to determine if scrapie was appearing in the inoculated sheep. The enquiry made the position clear. Scrapie was developing in the sheep vaccinated in 1935 and it was only in a few instances that the owner was associating the occurrence with louping-ill vaccination. The disease was affecting all breeds and it was confined to the animals vaccinated with batch 2. This was clearly demonstrated on a number of farms on which batch 1 had been used to inoculate the hoggs in 1935 and batch 2 to inoculate the ewes. None of the hoggs, which at this time were three- year-old ewes. At this time it was difficult to forecast whether all of the 18,000 sheep which had received batch 2 vaccine would develop scrapie. It was fortunate, however, that the majority of the sheep vaccinated with batch 2 were ewes and therfore all that were four years old and upwards at the time of vaccination had already been disposed of and there only remained the ewes which had been two to three years old at the time of vaccination, consequently no accurate assessment of the incidence of scrapie could be made. On a few farms, however, where vaccination was confined to hoggs, the incidence ranged from 1 percent, to 35 percent, with an average of about 5 percent. Since batch 2 vaccine had been incriminated as a probable source of scrapie infection, an attempt was made to trace the origin of the 112 sheep whose tissues had been included in the vaccine. It was found that they had been supplied by three owners and that all were of the Blackface or Greyface breed with the exception of eight which were Cheviot lambs born in 1935 from ewes which had been in contact with scrapie infection. Some of these contact ewes developed scrapie in 1936-37 and three surviving fellow lambs to the eight included in the batch 2 vaccine of 1935 developed scrapie, one in September, 1936, one in February, 1937, and one in November, 1937. There was, therefore, strong presumptive evidence that the eight Cheviot lambs included in the vaccine althought apparently healthy were, in fact, in the incubative stage of a scrapie infection and that in their tissues there was an infective agent which had contaminated the batch 2 vaccine, rendering it liable to set up scrapie. If that assumption was correct then the evidence indicated that:-
(1) the infective agent of scrapie was present in the brain, spinal cord and or spleen of infected sheep: (2) it could withstand a concentration of formalin of 0-35 percent, which inactivated the virus of louping-ill: (3) it could be transmitted by subcutaneous inoculation; (4) it had an incubative period of two years and longer.
Two Frenchmen, Cuille & Chelle (1939) as the result of experiments commenced in 1932, reported the successful infection of sheep by inoculation of emulsions of spinal cord or brain material by the intracerebral, epidural, intraocular and subcutaneous routes The incubation period varied according to the route employed, being one year intracerebrally, 15 months intraocularly and 20 months subcutaneously. They failed to infect rabbits but succeeded in infecting goats. Another important part of their work showed that the infective agent could pass throught a chamberland 1.3 filter, thus demonstrating that the infective agent was a filtrable virus. It was a curious coincidence that while they were doing their transmission experiments their work was being confirmed by the unforeseeable infectivity of a formalinized tissue vaccine.
As a result of this experience a large-scale transmision experiment involving the ue of 788 sheep was commenced in 1938 on a farm specially taken for the purpose by the Animal Diseases Research Association with funds provided by the Agricultural Research Council. The experiment was designed to determine the nature of the infective agent and the pathogenesis of the disease. It is only possible here to give a summary of the result which showed that (1) saline suspensions of brain and spinal cord tissue of sheep affected with scrapie were infective to normal sheep when inoculatted intracerebrally or subcutaneously; (2) the incubation period after intracerebral inoculation was seven months and upwards and only 60 percent of the inoculated sheep developed scrapie during a period of four and a half years; (3) the incubation period after subcutaneous inoculation was 15 months and upwards and only about 30 percent of the inoculated sheep developed the disease during the four and a half years: (4) the infective agent was of small size and probably a filtrable virus.
The prolonged incubative period of the disease and the remarkable resistance of the causal agent to formalin are features of distinct interest. It still remains to determine if a biological test can be devised to detect infected animals so that they can be killed for food before they develop clinical symptoms and to explore the possibilities of producing an immunity to the disease. ==================================================================
Greetings List Members,
pretty disturbing document. now, what would stop this from happening with the vaccineCJD in children???
kind regards, Terry S. Singeltary Sr., Bacliff, Texas USA
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.
sporadic CJD, the big lie
Thursday, July 10, 2008 A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008
Thursday, July 10, 2008 A New Prionopathy update July 10, 2008
MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE
Saturday, June 21, 2008 HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory JUNE 2008
Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA
NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 2007
Friday, July 18, 2008
TSE risk assessment from carcasses of ovine and caprine animals below 6 months of age from
TSE infected flocks intended for human consumption
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518