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Location: BACLIFF, Texas, United States

My mother was murdered by what I call corporate and political homicide i.e. FOR PROFIT! she died from a rare phenotype of CJD i.e. the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. sporadic, simply meaning from unknown route and source. I have simply been trying to validate her death DOD 12/14/97 with the truth. There is a route, and there is a source. There are many here in the USA. WE must make CJD and all human TSE, of all age groups 'reportable' Nationally and Internationally, with a written CJD questionnaire asking real questions pertaining to route and source of this agent. Friendly fire has the potential to play a huge role in the continued transmission of this agent via the medical, dental, and surgical arena. We must not flounder any longer. ...TSS

Thursday, August 20, 2015

Doctor William J. Hadlow

William J. Hadlow Dr. Hadlow (Ohio State ’48), 94, Hamilton, Montana, died June 20, 2015.

 

A past president of the American College of Veterinary Pathologists, he was a former head of the epidemiology branch of the National Institutes of Health’s Rocky Mountain Laboratory in Hamilton. Following graduation, Dr. Hadlow taught veterinary pathology at the University of Minnesota. In 1952, he joined RML as a veterinary pathologist, beginning a lifelong research career in comparative pathology. Dr. Hadlow transferred to the Animal Disease and Parasite Research Division of the Department of Agriculture's Agricultural Research Service in 1958, stationed in Berkshire, England. In 1961, Dr. Hadlow returned to the United States as a research pathologist and head of the slow viral disease section of the RML.

 

Dr. Hadlow was known for his expertise on prion disease pathology, playing a major role in identifying chronic wasting disease and bovine spongiform encephalopathy as prion diseases. He established a scrapie disease research program and investigated several other infectious diseases, including Aleutian disease of mink and progressive pneumonia of sheep. Dr. Hadlow’s research linked neurologic disorders in humans and animals, and his work contributed to the use of slow virus infections of animals as models for human disease. He identified kuru, a spongiform encephalopathy of New Guinea inhabitants, as a slow virus disease similar to scrapie, publishing his observations in an article in Lancet. On the basis of the article, Daniel C. Gajdusek, MD, received an NIH grant to investigate kuru and ultimately won a Nobel Prize for his work.

 

In 1971, Dr. Hadlow received a Superior Service Award from what is now known as the Department of Health and Human Services, and, in 1981, he was the recipient of a Distinguished Alumnus Award from The Ohio State University College of Veterinary Medicine. Dr. Hadlow was awarded the Olafson Medal, created to honor Dr. Peter Olafson, in 1992 for his contributions in pathology to the fields of comparative medicine and infectious disease, and, in 1994, he received the American Veterinary Epidemiology Society’s Karl F. Meyer Gold Headed Cane Award for outstanding contributions to veterinary epidemiology. In 2001, the University of Minnesota honored him with an honorary doctor of science degree for his achievements in veterinary medicine.

 

Dr. Hadlow was a veteran of the Army and the Navy. He is survived by his son and daughter.

 


 

IN CONFIDENCE

 

A STUDY AIMED AT DETERMINING WHETHER OR NOT THERE HAVE BEEN SIGNIFICANT CHANGES IN THE NEUROPATHOLOGY OF SCRAPIE IN SHEEP AND GOATS DURING THE LAST TWO DECADES IN MATERIAL SUBMITTED TO CVL PATHOLOGY DEPARTMENT.

 

SNIP...

 

CORTICAL LESIONS IN GOATS HAVE ALSO BEEN RECOGNISED AND HAD NOT PREVIOUSLY BEEN SEEN BY PROFESSOR BARLOW (WHO HAD SEEN VERY LITTLE NATURAL GOAT SCRAPIE ANYWAY), OR BY DR HADLOW. THE SIGNIFICANCE OF THIS IS UNCLEAR. THERE IS AT PRESENT NO EVIDENCE THAT CORTICAL LESIONS ARE CORRELATED WITH FEEDING PRACTICES. THE NUMBER OF GOAT SUBMISSIONS HAS BEEN MUCH LESS THAN THOSE OF SHEEP.

 

SNIP...END

 

PART A - THE RISK OF EXPOSURE THROUGH FEED.

 

How much feed is produced and consumed

 

Annual production figures for concentrate feed from 1980 to 1994 are summarised in Figure 1 and Tables 1-3.

 

snip...

 

ONE vital piece of information that is not held centrally is the extent to which meat and bone meal was used in sheep rations (see below).

 

snip...please see ;

 

THE RISK OF TRANSMISSION OF BSE TO SHEEP VIA FEED

 


 

Philos Trans R Soc Lond B Biol Sci. 2008 Nov 27;363(1510):3644. doi: 10.1098/rstb.2008.4013.

 

Kuru likened to scrapie: the story remembered.

 

Hadlow WJ.

 

PMID: 18849258 [PubMed - indexed for MEDLINE] PMCID: PMC2735530 Free PMC Article

 

 Clin Neurol Neurosurg. 2002 Jan;104(1):1-9.

 

Notes on the history of the prion diseases. Part I.

 

Poser CM1.

 

 Author information

 

 Abstract

 

The astute observation by William Hadlow, an American veterinary neuropathologist of the similarity between the histopathology of kuru, an obscure disease of the primitive tribe in New Guinea, and scrapie of sheep, was the first clue to the etiology of the transmissible spongiform encephalopathies (TSE). The knowledge that scrapie was transmissible but only after an unusually long incubation period, that the causative agent was highly resistant to heat and formalin, and that it seemed to be able to replicate in the absence of nucleic acid, eventually led to the discovery of the prion by Stanley Pruisner and the still controversial protein-only hypothesis of etiology of the TSE.

 

PMID: 11792469 [PubMed - indexed for MEDLINE]

 

Vet Pathol. 1999 Nov;36(6):523-9.

 

Reflections on the transmissible spongiform encephalopathies.

 

Hadlow WJ.

 

PMID: 10568433 [PubMed - indexed for MEDLINE] Free full text

 

J Comp Pathol. 1995 Oct;113(3):241-51.

 

Experimental infection of cattle with the agents of transmissible mink encephalopathy and scrapie.

 

Robinson MM1, Hadlow WJ, Knowles DP, Huff TP, Lacy PA, Marsh RF, Gorham JR.

 

 Author information

 

 Abstract

 

Cattle are susceptible to experimental infection with the Stetsonville isolate of the transmissible mink encephalopathy (TME) agent. To determine if they are susceptible to other TME isolates, two groups of calves were inoculated intracerebrally with homogenate of mink brain containing the Hayward isolate or the Blackfoot isolate. For comparison, a third group was inoculated with a brain homogenate from a steer infected with the Stetsonville isolate in its primary cattle passage and a fourth group was inoculated with a pool of brain homogenate from three cattle experimentally infected with a sheep and goat scrapie agent in its primary cattle passage. Clinical signs of neurological disease appeared in each steer of every group between 15 and 25 months after inoculation. An encephalopathy characterized by severe spongiform change and pronounced astrocytosis occurred in the three groups inoculated with the TME agent. In contrast, the neurohistological changes in the steers inoculated with the cattle-passaged scrapie agent were slight and subtle. Analysis of the octapeptide repeat region of the bovine protease-resistant protein (PrP) gene showed that variations in incubation period, clinical signs, and neurohistological changes were unrelated to the homozygous or heterozygous condition of six or six/five octapeptide repeats.

 

PMID: 8592050 [PubMed - indexed for MEDLINE]

 

Am J Vet Res. 1995 May;56(5):606-12.

 

Encephalopathy in cattle experimentally infected with the scrapie agent.

 

Clark WW1, Hourrigan JL, Hadlow WJ.

 

 Author information

 

 Abstract

 

Ten 8- to 10-month-old cattle were each inoculated intramuscularly, subcutaneously, intracerebrally, and orally with the scrapie agent to determine whether cattle are susceptible to it. Two inocula, both 10% homogenates of cerebrum, were used. One inoculum was from a sheep used for the second experimental ovine passage of the agent from 4 naturally affected Suffolk sheep. The other inoculum was from a goat used for the first experimental caprine passage of the agent from 2 naturally affected dairy goats living with the Suffolk sheep, the source of their infection. Between 27 and 48 months after inoculation, neurologic disease was observed in 1 of 5 cattle given the sheep brain homogenate and in 2 of 5 given the goat brain homogenate. In all 3 affected cattle, the disease was expressed clinically as increasing difficulty in rising from recumbency, stilted gait of the pelvic limbs, disorientation, and terminal recumbency during a 6- to 10-week course. Neurohistologic changes, though consistent with those of scrapie, were slight and subtle: moderate astrocytosis with sparse rod cells, some neuronal degeneration, a few vacuolated neurons, and scant spongiform change. Clinically and neurohistologically, the experimentally induced disease differed from bovine spongiform encephalopathy. The differences emphasize that such infections in cattle induce diverse responses, presumably depending largely on the strain of the agent. Pathologists should keep this variability in mind when looking for microscopic evidence of a scrapie-like encephalopathy in cattle.

 

PMID: 7661455 [PubMed - indexed for MEDLINE]

 

Brain Pathol. 1995 Jan;5(1):27-31.

 

Neuropathology and the scrapie-kuru connection.

 

Hadlow WJ.

 

Abstract

 

When their kinship was surmised 35 years ago, scrapie and kuru were linked mainly by their neuropathologic similarity. Most notable were neuronal degeneration and intense astrocytosis with little, if any, inflammation. Especially eye-catching in kuru were the vacuolated neurons--the histologic hall-mark of scrapie that drew me to the human disease from the start. Because spongiform change in gray matter neuropil is variable and usually lacks prominence in both scrapie and kuru, it was not part of the resemblance I saw in them. Amyloid plaques, so characteristic of kuru, also did not figure in the similarity, for they had not yet been reported in scrapie. Despite the uncertainty at the time about the pathologic essence of scrapie, the two diseases still looked alike. Their eventual connection--however tenuously held together initially by the few likenesses--has survived as a tribute to morphologic observation. It provided the essential link that helped ensure the kinship a lasting place in comparative neuropathology.

 

PMID: 7767488 [PubMed - indexed for MEDLINE]

 

J Gen Virol. 1994 Sep;75 ( Pt 9):2151-5.

 

Experimental infection of mink with bovine spongiform encephalopathy.

 

Robinson MM1, Hadlow WJ, Huff TP, Wells GA, Dawson M, Marsh RF, Gorham JR.

 

 Author information

 

 Abstract

 

To determine whether the aetiological agent of bovine spongiform encephalopathy (BSE) is pathogenic for mink, standard dark mink were inoculated with coded homogenates of bovine brain from the U.K. Two homogenates were from cows affected with BSE. The third was from a cow that came from a farm with no history of having had BSE or having been fed ruminant-derived, rendered by-products, the proposed vehicle for introduction of the BSE agent. Each homogenate was inoculated intracerebrally into separate groups of mink and a pool of the three was fed to a fourth group. Signs of neurological disease appeared in mink an average of 12 months after intracerebral inoculation and 15 months after feeding. Decreased appetite, lethargy and mild to moderate pelvic limb ataxia were the predominant clinical signs, quite unlike the classic clinical picture of transmissible mink encephalopathy (TME). Microscopic changes in brain sections of most affected mink were those of a scrapie-like spongiform encephalopathy. Vacuolar change in grey matter neuropil was accompanied by prominent astrocytosis. Varying greatly in severity from one mink to another, the degenerative changes occurred in the cerebral cortex, dorsolateral gyri of the frontal lobe, corpus striatum, diencephalon and brainstem. Although resembling TME, the encephalopathy was distinguishable from it by less extensive changes in the cerebral cortex, by more severe changes in the caudal brainstem and by sparing of the hippocampus. The results of this study extend the experimental host range of the BSE agent and demonstrate for the first time the experimental oral infection of mink with a transmissible spongiform encephalopathy agent from a naturally infected ruminant species.

 

PMID: 8077914 [PubMed - indexed for MEDLINE]

 

Bull Acad Natl Med. 1994 May;178(5):859-71.

 

[Natural history of transmissible subacute spongiform encephalopathy (TSSE)].

 

[Article in French]

 

Constantin A.

 

Abstract

 

Sheep Scrapie is the archetype of ESST It has been described for more than 200 years but the first scientific papers were published less than 60 years ago. The link between doctors and veterinary surgeons enabled our knowledge to develop. First, a Slow Virus was evoked, then Hadlow DVM (USA) suggested using brain filtrates from deceased patients of Kuru in order to inoculate primates or small rodents; this was carried out by the team of D.C. Gajdusek. The complete absence of immune reaction has made the label "slow Virus" give way to "Non Conventional Transmissible Agent" (NCTA). The few human cases of ESST have all been transmitted to mice, rats, hamsters... S.B. Prusiner (San Francisco) has given us an enormous boost with the notion of Prion, a protein molecule derived from an ordinary small membrane protein. Having recourse to transgenic mice has enabled American and European teams to demonstrate the essential role of genetics in the forming of the Transmissible Agent which is certainly Not Conventional. Those responsible for the Health of Cattle in U.K. will not contradict us. Future Research will be fascinating and will open a new chapter in the Medical Science concerning Mammals.

 

PMID: 7953894 [PubMed - indexed for MEDLINE]

 

Rev Sci Tech. 1992 Jun;11(2):539-50.

 

Transmissible mink encephalopathy.

 

Marsh RF1, Hadlow WJ.

 

 Author information

 

 Abstract

 

Transmissible mink encephalopathy (TME) is a rare disease of ranch-raised mink caused by exposure to an as yet unidentified contaminated food ingredient in the ration. The clinical and pathological similarities between TME and scrapie, together with the indistinguishable physicochemical characteristics of their transmissible agents, suggest that sheep may be the source of infection. However, experimental testing of oral susceptibility of mink to several different sources of sheep scrapie have been unsuccessful. These results indicate that either the feeding of scrapie-infected sheep tissues to mink is not the cause of TME, or that there exists a strain of sheep scrapie having high mink pathogenicity that remains unknown. Additional sources of sheep scrapie need to be tested in mink, and epidemiological investigations of new incidents of TME need to emphasise obtaining a thorough history of past feeding practices.

 

PMID: 1535524 [PubMed - indexed for MEDLINE]

 

J Am Vet Med Assoc. 1990 May 15;196(10):1676-7.

 

An overview of scrapie in the United States.

 

Hadlow WJ.

 

PMID: 2347765 [PubMed - indexed for MEDLINE]

 

J Virol. 1987 Oct;61(10):3235-40.

 

Temporal distribution of transmissible mink encephalopathy virus in mink inoculated subcutaneously.

 

Hadlow WJ, Race RE, Kennedy RC.

 

Abstract

 

Information was sought on the temporal distribution of transmissible mink encephalopathy virus in royal pastel mink inoculated subcutaneously with 10(3.0) 50% intracerebral lethal doses of the Idaho strain. As determined by intracerebral assay in mink, extremely little replication of the virus occurred during the preclinical stage of infection. It seemed largely limited to lymph nodes draining the site of inoculation. Virus first appeared in the central nervous system (CNS) at 20 weeks, when all mink were still clinically normal. Early spongiform degeneration, limited to the posterior sigmoid gyrus of the frontal cortex, was first found at 28 weeks, or a few weeks before onset of clinical disease in most of the mink. Once virus reached the CNS, where greater concentrations occurred than elsewhere, it appeared in many extraneural sites (spleen, liver, kidney, intestine, mesenteric lymph node, and submandibular salivary gland). These seemingly anomalous findings, especially the limited extraneural replication of virus as a prelude to infection of the CNS, suggest that mink are not natural hosts of the virus. The results of this study support the generally held view that transmissible mink encephalopathy arises from chance or inadvertent infection of ranch mink with an exogenous virus, most likely feed-borne wild scrapie virus.

 

PMID: 2957510 [PubMed - indexed for MEDLINE] PMCID: PMC255903 Free PMC Article

 

Select item 2952237 12.

 

Can J Vet Res. 1987 Jan;51(1):135-44.

 

Experimental infection of sheep and goats with transmissible mink encephalopathy virus.

 

Hadlow WJ, Race RE, Kennedy RC.

 

Abstract

 

In a study to learn more about the pathogenicity of transmissible mink encephalopathy virus for the natural hosts of scrapie, 20 Cheviot sheep and 19 dairy goats were inoculated intracerebrally with the Idaho strain of the virus. Five sheep and nine goats became affected with a progressive neurological disease. The incubation period in the sheep varied from 45 to 80 months (mean, 65 months) and in the goats from 31 to 40 months (mean, 35 months). Except for degeneration of the cerebral cortex (neocortex), the disease was indistinguishable clinically and neurohistologically from scrapie. During two more passages of the virus in goats, the incubation period was shortened to 12 to 15 months, the morbidity rate rose to 100% (6/6 dairy goats and 3/3 African pygmy goats), and the cortical lesion became constant and more pronounced. By the intracerebral inoculation of pastel mink, transmissible mink encephalopathy virus was detected in the brains of several affected sheep and goats but not in extraneural sites (lymphoid tissues and intestine), except for a trace amount in the proximal colon of one goat. Even after two passages in goats, the virus remained nonpathogenic for the laboratory mouse. Despite the essential likeness of the experimental disease and scrapie, the common identity of their causal viruses remains to be determined. Even so, the results of this study are still compatible with the view that transmissible mink encephalopathy virus almost certainly is scrapie virus whose biological properties became altered by chance passage in mink, a carnivore and an aberrant host.

 

PMID: 2952237 [PubMed - indexed for MEDLINE] PMCID: PMC1255287 Free PMC Article

 

Vet Pathol. 1986 Sep;23(5):543-9.

 

Cerebrocortical degeneration in goats inoculated with mink-passaged scrapie virus.

 

Hadlow WJ, Race RE.

 

Abstract

 

Widespread spongiform degeneration of the cerebral cortex occurred in four African pygmy goats that became affected with scrapie after intracerebral inoculation with scrapie virus (Suffolk sheep brain origin) that had been passed three times in ranch mink. The occurrence of such cerebrocortical degeneration was a distinct departure from the topographic pattern of neuropathologic changes that characterizes scrapie in sheep and goats. But the cortical lesion was identical to the one found in goats that became affected with a disease otherwise indistinguishable from scrapie after intracerebral inoculation with transmissible mink encephalopathy (TME) virus that had been passed twice in mink. If TME originated from infection with wild scrapie virus, as is generally thought, then the viruses used in these two instances would be equivalent in their passage history in this aberrant host. Given this similarity, the common occurrence of the cortical lesion is thought to be consistent with the view that TME virus almost certainly is scrapie virus whose biologic properties became altered by chance passage in ranch mink.

 

PMID: 2946103 [PubMed - indexed for MEDLINE] Free full text

 

Am J Vet Res. 1984 Dec;45(12):2637-9.

 

Experimental infection of fetal and newborn Suffolk sheep with scrapie virus.

 

Hadlow WJ, Jackson TA, Race RE.

 

Abstract

 

Fetal (n = 21) and newborn (n = 7) Suffolk sheep were inoculated with scrapie virus isolated from other Suffolk sheep. Twenty fetuses, 76 to 109 days of gestational age, were inoculated IM in the neck through the uterine wall and were examined for virus 47 to 322 days later by mouse inoculation. Scrapie virus was not detected before 254 days of age; only traces of virus were detected in 3 of 7 lambs examined thereafter (2 at 254 days of age and 1 at 322 days of age). Virus was limited to the supra-pharyngeal, prescapular, and mesenteric lymph nodes. Seven lambs were inoculated into the palatine tonsils with scrapie virus as newborns (3 to 12 days old) and were examined for virus when they were 147 to 210 days old. Virus was not detected in the lymphoreticular tissues or terminal portion of ileum of any lamb. Failure to find scrapie virus in these lambs and in most lambs inoculated as fetuses might indicate few had became infected. However, if most lambs and fetuses had become infected, the long zero phase of the infection could have accounted for failure to find scrapie virus in many of them examined too soon after inoculation. The limited findings of this study indicate that efforts to demonstrate prenatal or neonatal transmission of scrapie by detecting virus are hampered by the slowness of its replication.

 

PMID: 6441491 [PubMed - indexed for MEDLINE]

 

J Infect Dis. 1982 Nov;146(5):657-64.

 

Natural infection of Suffolk sheep with scrapie virus.

 

Hadlow WJ, Kennedy RC, Race RE.

 

Abstract

 

A better understanding of the infectious process in scrapie was sought by studying the temporal distribution of virus in naturally infected Suffolk sheep. Virus was detected (by mouse inoculation) first in lymphatic tissues and intestine of clinically normal lambs (age, 10-14 months). Titers were generally low. Infection of the central nervous system was first detected in a 25-month-old clinically normal sheep whose nonneural tissues had moderate amounts of virus. In sheep affected with scrapie, similar amounts in nonneural tissues accompanied high concentrations in the central nervous system, notably in sites of severest neurohistologic changes. No virus was found in clinically normal high-risk sheep 54 to 104 months old. The early appearance of virus in tonsil, retropharyngeal and mesenteric-portal lymph nodes, and intestine suggests that primary infection occurs by way of the alimentary tract, either prenatally from virus in amniotic fluid or postnatally from virus in a contaminated environment.

 

PMID: 6813384 [PubMed - indexed for MEDLINE]

 

Ann Neurol. 1980 Dec;8(6):628-32.

 

Brain tissue from persons dying of Creutzfeldt-Jakob disease causes scrapie-like encephalopathy in goats.

 

Hadlow WJ, Prusiner SB, Kennedy RC, Race RE.

 

Abstract

 

Two goats became affected with an encephalopathy indistinguishable from scrapie 43 months after they were inoculated intracerebrally with 10% suspensions of brain from two persons dying of Creutzfeldt-Jakob disease. Although this observation does not establish the common identity of Creutzfeldt-Jakob disease virus and scrapie virus, it is thought to provide strong evidence of a close etiological relationship between the two diseases.

 

PMID: 7011169 [PubMed - indexed for MEDLINE]

 

J Neurochem. 1980 Sep;35(3):574-82.

 

Experimental scrapie in the mouse: electrophoretic and sedimentation properties of the partially purified agent.

 

Prusiner SB, Garfin DE, Cochran SP, McKinley MP, Groth DF, Hadlow WJ, Race RE, Eklund CM.

 

Abstract

 

Some biochemical and biophysical properties of the scrapie agent in a partially purified fraction P5 from murine spleen are described in this communication. The agent was stable in the nonionic detergents Triton X-100 and Nonidet P40 and stable in the nondenaturing, anionic detergents sodium cholate and sodium N-lauroyl sarcosinate. In contrast, sodium dodecyl sulfate (SDS) inactivated the agent at high concentrations (1% or >) when the detergent-to-protein ration approached 1.5 g SDS/g protein. The agent was resistant to inactivation by nucleases and proteases, even in the presence of 0.1% SDS. A broad peak of infectivity was exhibited in modified colloidal silica (Percoll) density gradients. Maximal titers were found at a Percoll density of 1.10 g/cm3 in the presence and absence of 0.05% SDS. Gel electrophoresis of the agent in the presence of 0.1% SDS resulted in inactivation of > 95% of the agent loaded onto the gel. Free-flow electrophoresis showed that > 99% of the agent in fraction P5 migrated toward the anode, but not as a discrete species. Sedimentation analysis of the agent in fraction P5 in the presence of 1% lysolecithin showed that the agent has a sedimentation coefficient of < 300S but > 30S. Heating P5 preparations caused the agent to associate with cellular elements and form aggregates with sedimentation coefficients > 10,000S. Removal by differential centrifugation of the large forms of the agent produced upon heating permitted characterization of a discrete subpopulation of scrapie agent particles. Rate-zonal sucrose gradient studies showed that > 95% of the infectivity in this subpopulation sedimented as uniform particles with a sedimentation coefficient of 240S.

 

PMID: 6778963 [PubMed - indexed for MEDLINE]

 

Vet Pathol. 1980 Mar;17(2):187-99.

 

Virologic and neurohistologic findings in dairy goats affected with natural scrapie.

 

Hadlow WJ, Kennedy RC, Race RE, Eklund CM.

 

Abstract

 

Virologic and neurohistologic findings in three dairy goats that became affected with scrapie while living with naturally infected Suffolk sheep were essentially like those in affected sheep. Virus, detected by mouse inoculation, was widespread in non-neural sites, particularly in lymphatic tissues and intestine. Im most sites, titers of virus ranged from 3.0 to 3.5 log10 mouse intracerebral LD50/30 mg of tissue. Virus was in nervous tissue in much higher titer. Ranging from 5.1 to 5.8 log10, the highest mean titers were in the diencephalon, midbrain, medulla oblongata and cerebellar cortex--sites of the most severe histologic changes. Although these changes were like those in naturally affected Suffolk sheep, they differed somewhat from those in goats affected with the experimental disease. Spongiform alteration of neuropil was minimal, and the more rostral parts of the brain, such as corpus striatum, globus pallidus and septal area, had few changes. Concentrations and distribution of virus in non-neural tissues were consistent with the conclusion that scrapie virus no doubt can be maintained by contagion in a herd of goats living apart from infected sheep.

 

PMID: 6767304 [PubMed - indexed for MEDLINE] Free full text

 

Prog Clin Biol Res. 1980;39:73-89.

 

Slow viruses: molecular properties of the agents causing scrapie in mice and hamsters.

 

Prusiner SB, Cochran SP, Baringer JR, Groth D, Masiarz F, McKinley M, Bildstein C, Garfin D, Hadlow WJ, Race RE, Eklund CM.

 

PMID: 6773068 [PubMed - indexed for MEDLINE]

 

Biochemistry. 1978 Nov 14;17(23):4987-92.

 

Sedimentation characteristics of the scrapie agent from murine spleen and brain.

 

Prusiner SB, Hadlow WJ, Eklund CM, Race RE, Cochran SP.

 

Abstract

 

Sedimentation profiles of the scrapie agent in extracts of murine spleen and brain were determined by analytical differential centrifugation. Infectivity profiles of the agent from the two tissues were similar. Sedimentation of the agent was not substantially altered by detergent treatment with sodium deoxycholate. In the presence of detergent, centrifugation at an omega2t value of 3.0 x 1010 rad2/s in a fixed-angle rotor sedimented 90% of the agent. Comparative studies with radioisotopically labeled Simian virus 40 showed that centrifugation at an omega2t value of 1.6 x 10(10) rad2/s removed 90% of the virions. The sedimentation profile of the scrapie agent was similar to that observed for cellular ribosomal RNA. Heating infectious extracts of spleen to 80 degrees C for 30 min resulted in the destruction of 95% of the RNA while sedimentation of the scrapie agent was unchanged. These studies establish a limited range of particle sizes for the scrapie agent.

 

PMID: 214106 [PubMed - indexed for MEDLINE]

 

Biochemistry. 1978 Nov 14;17(23):4993-9.

 

Partial purification and evidence for multiple molecular forms of the scrapie agent.

 

Prusiner SB, Hadlow WJ, Garfin DE, Cochran SP, Baringer JR, Race RE, Eklund CM.

 

Abstract

 

A procedure for the partial purification of the scrapie agent from mouse spleen was developed based on its sedimentation profile. Differential centrifugation and detergent treatment with sodium deoxycholate yielded a fraction designated "P5" which was enriched for scrapie infectivity approximately 20-fold with respect to cellular protein. The P5 fraction was devoid of cellular membranes but heavily contaminated with ribosomes as judged by electron microscopy. On centrifugation of the fraction P5 to near equilibrium in a sucrose gradient scrapie infectivity was distributed over a range of densities from 1.08 to 1.30 g/cm3. Parallel rate-zonal analysis showed that the infectivity was distributed over a range of particle sizes with s20.w values from approximately 40 S to greater than 500 S. Incubation of P5 at 37 or 80 degrees C, under conditions that disrupt ribosomes, dramatically altered the rate-zonal gradient profile of the agent. Under these conditions, the agent sedimented as particles with s20.w greater than 500 S. The apparent heterogeneity of the scrapie agent with respect to both size and density and its ability to shift from one form to another suggest that the agent may contain hydrophobic domains on its surface.

 

PMID: 102338 [PubMed - indexed for MEDLINE]

 

Trans Am Neurol Assoc. 1978;103:62-4.

 

Evidence for hydrophobic domains on the surface of the scrapie agent.

 

Prusiner SB, Garfin DE, Cochran SP, Baringer JR, Hadlow WJ, Eklund CM, Race RE.

 

PMID: 117582 [PubMed - indexed for MEDLINE]

 

Proc Natl Acad Sci U S A. 1977 Oct;74(10):4656-60.

 

Sedimentation properties of the scrapie agent.

 

Prusiner SB, Hadlow WJ, Eklund CM, Race RE.

 

Abstract

 

The sedimentation behavior of the scrapie agent in homogenates of spleen from infected mice has been determined. Approximately 90% of the scrapie agent was sedimented at an omega2t value of 3 X 10(10) rad2/sec in a fixed-angle rotor. Sedimentation of the agent was not substantially affected by sonication or by treatment with the detergent sodium deoxycholate. The sedimentation profiles of the scrapie agent were similar to those observed for free polyribosomes, but differed from those exhibited by five other subcellular markers. Comparative studies showed that the sedimentation profiles of subcellular markers in spleen suspensions from mice infected with scrapie did not differ from uninoculated controls. These studies suggest that the scrapie agent is a discrete infectious particle which should be separable from cellular membranes.

 

PMID: 412193 [PubMed - indexed for MEDLINE] PMCID: PMC432006 Free PMC Article

 

J Infect Dis. 1974 May;129(5):559-67.

 

Course of experimental scrapie virus infection in the goat.

 

Hadlow WJ, Eklund CM, Kennedy RC, Jackson TA, Whitford HW, Boyle CC.

 

PMID: 4207308 [PubMed - indexed for MEDLINE]

 

Medicine (Baltimore). 1973 Jul;52(4):357-61.

 

Implications of slow viral diseases of domestic animals for human disease.

 

Eklund CM, Hadlow WJ.

 

PMID: 4578994 [PubMed - indexed for MEDLINE]

 

Infect Immun. 1972 Mar;5(3):319-23.

 

Isolation from mouse spleen of cell populations with high specific infectivity for scrapie virus.

 

Lavelle GC, Sturman L, Hadlow WJ.

 

Abstract

 

Spleen cells from mice infected with scrapie virus were separated into subpopulations on the basis of buoyant density in discontinuous gradients of isotonic albumin or differential adherence of cells to plastic. At three different intervals after infection, a population of "less dense" cells was found in albumin gradients that had 40-to 60-fold higher specific infectivity (cells per median lethal dose) than the total cell suspension before gradient sedimentation. The class of cells associated with high relative specific infectivity has a density characteristic of lymphoblasts, myeloblasts, and macrophages. Separation of "macrophage rich" cells on the basis of adherence to plastic did not result in significant enrichment of scrapie virus-infected cells.

 

PMID: 4629076 [PubMed - indexed for MEDLINE] PMCID: PMC422368 Free PMC Article

 

J Am Vet Med Assoc. 1969 Dec 15;155(12):2094-9.

 

Pathogenesis of slow viral diseases.

 

Eklund CM, Hadlow WJ.

 

PMID: 5392180 [PubMed - indexed for MEDLINE]

 

Res Publ Assoc Res Nerv Ment Dis. 1968;44:281-306.

 

Scrapie--a virus-induced chronic encephalopathy of sheep.

 

Hadlow WJ, Eklund CM.

 

PMID: 4978853 [PubMed - indexed for MEDLINE]

 

J Infect Dis. 1967 Feb;117(1):15-22.

 

Pathogenesis of scrapie virus infection in the mouse.

 

Eklund CM, Kennedy RC, Hadlow WJ.

 

PMID: 4961240 [PubMed - indexed for MEDLINE]

 


 

The case for mad pigs in the US

 

From the Consumer Policy Institute and Consumers Union: March 24, 1997

 

Stephen F. Sundlof, D.V.M., Ph.D

 

Center for Veterinary Medicine Food and Drug Administration 7500 Standish Place, Room 482, HFV 1 RockvLIle, MD 20855

 

Dear Dr. Sundlof:

 

We are writing to you to submit information that has recently come to our attention which suggests that a TSE like disease (transmissible spongiform encephalopathy) might exist in pigs in the U.S. We believe this new informantion calls for intensive research and makes it urgent to ban the use of all mammalian proteins, including swine, in the feed of all food animals, until better answers are found.

 

The evidence for the potential PSE (porcine spongiform encephalopathy ) is as follows. In 1979, an FSQS veternarian, Dr. Masuo Doi, noticed some unusual central nervous system (CNS) symptoms in young (about 6 months old) hogs coming into a slaughter plant In Albany, New York. Since the plant received hogs from a wide variety of sources (New York, Canada, Indiana, Illinois, Ohio, and other Midwestern states) and was not a plant used to dealing with diseased animals, Dr. Doi thought that the problem might be affecting hogs slaughtered nationwide. So, he decided to conduct a detailed study on central nervous system (CNS) symptoms/disease in young hogs coming into that slaughter plant. The study ran for 15 months (January, 1979 to March, 1980) and consisted of extended observations of the behavior of animals with suspected CNS symptoms at the plant, followed by pathological, histopatholpgical, and microbiological work on tissues from various organs of particular animals after slaughter.

 

For his behavioral observational work, Dr. Doi extended the usual two day observation period to three to four days, during which he took careful notes on the animals' behavior and other vital signs. During the 15 month period of the study, some 106 animals exhibiting CNS symptoms were retained during antemortem inspection.

 

A 1980 paper that summarized Dr. Doi's findings on the clinical symptoms and incidence of the 'disease," contained descriptions of these symptoms that sound remarkably similar to the symptoms noted for bovine spongiform encephalopathy (BSE):

 

"Excitable or nervous temperament to external stimuli such as touch to the skin, handling and menacing approach to the animals is a common characteristic sign among swine affected with the disease.... In the advanced stage of the disease, manifestation of neurological signs are evidenced in the form of general ataxia . . . Many animals have been found to be "downers' at first observation; if the hindquarters of these downers are raised they may be able to walk one or two steps and then fall to the ground" (Doi et al., 1980: 2, 4). Indeed, a table of symptoms includes, for the early stage: "excitability and nervousness (squealing, smacking of lips, grinding of teath, chewing, gnawing ant foaming at mouth); stiffness of limbs . . . 'tic'; weakness of hindquarters; focal tremors of skeletal muscles"; and for the advanced stage: depression; ataxia; crossing over of limbs . . . kneeling posture . . . crawling". In addition to his clinical observations, Dr. Doi also made an 8 mm film of thirteen of the affected animals; film of two of the pigs was shown at the MPI National Pathology Meeting in Seattle, Washington on flay 20, 1979.

 

Dr. Doi sent tissue samples from suspect cases to the USDA's Eastern Laboratory in Athens, GA for pathological, histopathogical and microbiological work. Known infectious diseases were ruled out. As Dr. Doi points out, "Histopathological studies of tissue collected from the brain and spinal cord of these animals in the early stage of the disease show congestion, hemorrhage and neuronal degeneration. All animals in the advanced stage of the disease have been confined to have Encephalitis or Meningitis by MPI laboratory" (Doi et al., 1980: 5). Eventually some 60 animals were confirmed by the MPI Laboratory to have encephalitis or meningitis, with no ldentifiable cause. As pointed out in a paper presented at the 1979 MPI National Pathology Meetings,

 

"Since January, a number of hogs in this establishment have been found, in antemortem, to show what appears to be CNS. Sets of tissue samples were sent to the laboratory for examination, various tests were done which include histological study (E H stain), fluorescence antibody technique, virus neutralization and viral and bacteriological isolation. Differential diagnosis was also done to exclude vitamin B deficiency, post vaccination reaction, chlorinated hydrocarbon, arthritis, and transport stress" (Doi et al., 1979). The brains of the 60 animals were examined. The brain of one of these pigs, on histopathological analysis, exhibited signs reminiscent of a TSE. This histopathological work was performed by Dr. Karl Langheinrich, Pathologist-In-Charge at USDA's Eastern Laboratory in Athens, Georgia. According to the USDA FSQS laboratory report, dated early November, 1979, Dr. Langheinrich noted:

 

"Microscopic examination of the barrow tissues revealed a encephalopathy and diffuse gliosis characterized by vacuolated neurons, loss of neurons and gliosis in a confined region (nucleus) of the brain stem (anterior ventral midbrain). Only an empty sometimes divided vacuole was present instead of the normal morphology of a nerve cell. Occasionally a shriveled neuron was seen. According to . . . Pathology of Domestic Animals, . . . 'The degeneration of neurons, the reactivity of the glia .... are the classical hallmarks of viral infection of the central nervous system' .... Scrapie of sheep, and encephalopathy of mink, according to the literature, all produce focal vacuolation of the neurons similar to the kind as described for this pig. I was unable to locate any lead as to the cause of this interesting phenomenon in other species including swine'' (Langheinrich, 1979). Indeed, Dr. Langheinrich's main diagnosis was, " Encephalopathy and diffuse gliosis of undetermined etiology." Portions of the brain were sent for microbiological testing to a neurologist at the University of Georgia, where they came up negative for pseudo-rabies. The brain was unique enough that USDA scientists, such as Dr. Langheinrich and Or. Dot, mentioned it to student and scientific colleagues over the years.

 

In 1979-1980, BSE was completely unknown. However, both the behavior of the pigs, as well as the histopathology on at least one pig, both showed sign consistent with a porcine TSE. This raises particular concern became the affected animal was only 6 months old; in an animal this young, one would rust expect to see any physical signs of TSE in the brain. Histopathology of TSEs can be very variable, so that spongiform appearance (i.e. vacuolated neurons) are not always present. Behavioral changes can be seen in TSE-infected animals before any changes in brain morphology are visible. Dr. Clarence Gibbs, in testimony before a Congressional hearing on the TSE issue on January 29, 1997 made just this point:

 

''In the mid-1960s, we demonstrated with our French and English collaborators that during the early incubation of the TSEs, when the virus titer in the brain was very low, there were already marked functional changes, even though no pathology was yet detectable, even ultrastructurally. A month or hero later, polynucleation of neurons appeared in spider monkeys, incubating kuru, and somewhat later, microvacuolation and membrane changes visible only by electron microscopy. This preceded the pest appearance of astrogliosis and spongiform change. It was only much later that the classical scrapie TSE pathology appeared with virus titers in brain of 10 -5 or higher" (Gibbs, 1997; pg. 4). Given that TSEs can cause behavioral changes in infected animals before any physical changes in the brain can be seen, that the manifestation of TSE in the brain can be quite variable, and that changes in brain morphology are not usually seen in 6 month old animals, we are concerned that the brain of one pig actually showed physical evidence consistent with a TSE.

 

Following the announcement In March, 1996 of ten cases of new variant CJD (Creutzfeldt-Jakob Disease) in the United Kingdom and their possible connection to BSE, Drs. Doi, Langheinrich and others urged reinvestigation of this case.

 

In August, 1996, the USDA sent five slides, one of which was a histopathology slide, to Dr. Janice Miller of USDA's Agricultural Research Servicer . Dr. Miller stained four of the slides for prion protein (she didn't stain the H&E slide). Dr. Miller told Consumers Union that Dr. Patrick McCaskey, USDA/FSIS, in charge of the Research Center at Athens, GA, called her, told her that he had five slides that all showed "problems" and asked her to stain four of them. The H&E slide, which clearly show vacuoles in the neurons (one sign of TSE), wasn't stained because to stain for PrP entails removing the slide cover, baking the slide to destain it and then restaining it for PrP; they didn't want to risk destroying the H&E slide.

 

Dr. Doi had kept frozen samples of the brain and spinal chord of the suspect PSE pig in case the Eastern lab wanted more material for analysis. Unfortunately, these samples were discarded when the packing plant in Albany, NY closed in 1991. It appears that the brain material sent to the Univcrsity of Georgia may have been discarded. [pers com.. Dr. Doi 3/13/97]

 

Dr. Miller found that the PrP stained in the four pig slides was found only on the inside of neurons, while a positive control slide from a scrapie sheep showed massive amounts of extraneuronal staining. In a letter summarizing her results (copy attached), she concludes that the PrP stained in this pig was normal: "In the pig sections you will see a small particulate type of staining that is confined to neurons and as I indicated on the phone, I would interpret as normal PrP. It is in marked contrast to the massive amount of extraneuronal staining seen in the scrapie section" (Miller, 1996).

 

Unfortunately, Dr. Miller's finding toes not conclusively rule out a TSE. We are concerned that while British BSE and serapie create a massive amount of extraneuronal staining, there are TSEs where this isn't the case. Three experiments were done in He U.S. -- in Mission, TX (APHIS work), Pullman, Washington (ARS work), and Ames, Iowa (ARS work) -- to see whether sheep scrapie can possibly infect cows. In all the experiments, cattle were inoculated with tissue from scrapie -infected sheep primarily by intra-cranial injection, but in the case of the Texas and Iowa studies also by oral feeding -- to see if cattle were susceptible to scrapie at all. In all three experiments, the majority of cows injected in the brain with scrapie-infected sheep material (usually brains) also developed a fatal spongiform encephalopathy.

 

However, in all three examples, the symptoms of the spongifonn encephalopathy differed from "mad cow" disease ~ England, as did the appearances of slides from their brains. The brain lesions seen in ail these animals were more variable than those seen in England. When Dr. Miller did similar staining for PrP from these brains (what she called "bovine scrapie") she only found PrP stains on the inside of the neurons, not the massive extraneuronal staining seen in BSE (Miller, pers. comm., March 7, 1997). Thus, Dr. Miller's finding of PrP stains only inside the neurons in the suspect pigs is not particularly reassuring.

 

In November 1996, USDA sent the single histopathology slide to Dr. William Hadlow, one of the foremost spongiform encephalopathy pathologists in the world. (For unknown reasons, Dr. Hadlow was only sent the one slide; he was not told of the existence of the other slides, nor of Dr. Miller's findings, nor was he told or given the behavioral report from Dr. Doi or the morphology work by Dr. Langheinrich, or shown film of the affected pigs [Dr. Hadlow, pers. com., 3/13/97] From this single slide, Dr. Hadlow found some evidence consistent with TSEs but not enough for a conclusive diagnosis. He noted that the slide contained vacuoles inside neurons, one of the signs of a TSE (Dr. Langheinrich had noted this as well).

 

However, since such vacuoles occasionally occur normally in pigs, he thought that was not something special: "About twelve (12) neurons in the parasympathetic nucleus have unilocular optically empty vacuoles in the perikaryon. This is the site where such vacuolated neurons have been seen in the swine (as well as in cats and sheep) as an incidental finding. So I do not think such cells have any significance in this pig" (Hadlow, 1996). However, he did see evidence, Including changes in astrocytes, that suggested a TSE, but without examining other parts of the brain to look for other evidence of TSE, he couldn't be sure:

 

"I am impressed, though, with what seems to be an increase in the number of astrocytes in the section. Some astrocytes are in clusters, some are enlarged and vesicular. Where they are most numerous, a few rod cells (activated microglia) are seen. These findings suggest some perturbation of the nervous tissue. Although such a global response occurs in the transmissible spongifonn encephalopathies, I do no! know its significance in this case without examining other parts of the brain for changes characteristic of these diseases. Thus, from looking; at this one (1) section of brain, I cannot conclude that the pig was affected with a scrapie-like spongiform encephalopathy" (Hadlow, 1996). In sum, Dr. Hadlow~s letter does not rule out the possibility of a TSE. He says that there is suggestive evidence, but that he would need to look at other slides/sections of the brain, to make a conclusive diagnosis.

 

In our view, the implications of this data are extremely serious. Experiments in the United Kingdom have shown that pigs are susceptible to BSE. Pigs inoculated with BSE develop a TSE (Dawson et al., 1990). Feeding experiments are underway in the UK to see if BSE can be orally transmitted to pigs; as of March, 1997, some 6 years after the start of the experiment, none of the pigs fed BSE brain have come down with a TSE. Unfortunately the design of this experiment severely limits what we will learn from it, and will most likely not tell us conclusively if pigs can get BSE from feed. It turns out that the pigs were not fed BSE brain continuously. Rather, the pigs were only fed BSE brain material on three days, over a three week period (i.e.. one day each week). Following these three doses, the pigs were never fed contaminated material again. The total amount of infective material given to the pigs was therefore quite small. Thus, a negative finding would be hard to interpret and would not mean that BSE is not orally active in pigs.

 

We believe that as a top priority USDA should conduct follow-up studies to look for potential CNS/PSE cases in pigs (we plan to communicate about this to USDA separately). In brief, we feel that the following kinds of studies need to be done:

 

i) TSE pathology experts should examine all the slides from the suspect pig (2709). To our knowledge, at least 12 separate slides exist.

 

ii) Determine if any brain material from the suspect pig (2709) still exists at the Unlverslty of Georgia. If so, this material should be retrieved and used for transmission studies. In particular, suckling pigs should be inoculated with the material and then permitted to live unto they die of a disease or old age, at which point their brains should be examined for physical signs of a TSE as well as for immunchistochemical evidence (i.e. staining looking for the abnormal PrP).

 

iii) Increase antemortem inspection for CNS symptoms at hog facilities. Inspectors should be trained to detect the subtle CNS symptoms seen in the Doi et al. study. At a select number of slaughter facilities, animals exhibiting CNS symptoms should be removed and held for observation until they die, at which time their brains should be examined for evidence of a TSE.

 

iv) Research on CNS symptoms among Me 6,000 or so breeding sows which are permitted to live for 3+ years. Sows exhibiting CNS symptoms should be removed and held for observation until they die, at which time then brains should be exernined for evidence of a TSE.

 

While such work is underway, given the above inforrnabon, we believe that as a precutionary measure the FDA must expand the proposed ruminant plus mink-to-ruminnant feed ban to prevent protein from any material, including hogs, being fed to any food animal.

 

Sincerely,

 

Michael Hansen, Ph.D Research Associate

 

Jean Halloran Director

 

References

 

Dawson, M., Wells, G.A.H., Parker, B.N;J. and A.C Scott. 1990. Primary parental transmission of bovine spongiform encephalopathy to the pig. Veternary Record, pg. 338.

 

Doi, M., Matzner, N.D. and C. Rothaug. 1979. Observation of CNS disease in market hogs at Est. 893 Tobin Packing Co., Inc. Albany, New York. United States Department of Agriculture, Food Safety and Quality.Service, Meat and Poultry Inspection Service. 7pp.

 

Doi, M, Langheinrich, K. and F. Rellosa. 1980. Observations of CNS signs in hogs at Est. 893 Tobin Packing C:o., Inc. Presented by Dr. Lngheinrich at the MPI National Pathology Meeting in Seattle, Washington on July 20, 1979.

 

Gibbs, C. 1997. Statement to the Committee on Governnent Reform and Oversight, Subcommittee on Human Resources and Intergovernmental Relations, U.S. House of Representatives. January 29,1997.

 

Hadlow, WJ. 1996. Letter to Patrick McCaskey, USDA/FSIS/Eastem Lab, dated November 13, 1996.

 

Langheinrich, KA. 1979. USDA/FSQS Laboratory report on specimen 2709. Dated November 8, 1979

 

Miller, J. 1996. Letter to Patrick McCaskey, USDA/ESIS/Eastern Lab, dated September 6, 1996.

 

Dr. Janice Miller, ARS< USDA responds Mon, 31 Mar 1997 Correspondence My involvement in the "pig incident" (I refuse to say "mad pig disease" since no such disease has been recognized):

 

I was asked by Dr. Al Jenny at the National Veterinary Services Laboratory if I had ever done immunohistochemistry on slides that had already been stained by hematoxylin and eosin, the standard stain used for histopathology. I had done it on a few scrapie cases so he asked if I would do the procedure on some pig brain slides that he had received from Dr. Pat McCaskey, an FSIS pathologist in Athens, GA.

 

At the time I didn't know the history of the situation but Dr. Jenny said I should call Dr. McCaskey and discuss it with him before proceeding. Only then did I learn a little about the history of the case. We decided that I wouldn't try to stain all of the slides because I was afraid the procedure required to remove the cover slips might damage the sections and Dr. McCaskey was concerned about preserving the sections for other pathology consultations, if necessary.

 

We agreed that I would stain 4 of the 5 slides, leaving the slide with the best lesions untouched. I was also concerned that I didn't know whether the antiserum we use would stain pig PrP but decided it was worth a try. When I completed the staining procedure the only positive material I observed was a small amount of particulate staining within the cell body of some neurons. We have occasionally observed that kind of staining in brains from control cattle and sheep in our experiments and interpret it to be normal PrP. (A similar finding was reported by Dr. Haritani, who first described the technique for BSE).

 

That observation was reported in our 1994 paper and we stated that consequently we could not interpret intraneuronal staining as indicative of scrapie (although it may be present, the bulk of staining is in neuropil, around vessels and neurons, etc). In that study I think our interpretation was somewhat validated by the very close correlation we had between immunohistochemistry and western blot results. At any rate, I told Dr. McCaskey that my interpretation on the slides was that the only staining present was consistent with normal PrP. The good news was that the antiserum did in fact stain something and that it was in the correct location for normal PrP, indicating that the antiserum would have detected abnormal PrP, had it been present. Subsequently, I called Dr. Richard Rubenstein, who provided the antibody we use, and asked if he knew whether it would react with pig PrP and he said he didn't know. However, he said it reacted with almost all mammalian species, except ferret and mink, that he had tried so he would be surprised if it wasn't reactive with pig PrP.

 

So, having all of this information at hand, people can decide whether the immunohistochemical test means anything or not. The lack of a positive control pig tissue (positive sheep tissue is included in every test) may be viewed by some people as diminishing the value of a negative result, but feel we did the best we could under the circumstances.

 

The above recitation describes my experience with the case in question. I did not photograph the slides and returned all 5 to Dr. McCaskey. It was later that he had Dr. Hadlow look at the case for histopathologic interpretation. I did not examine the slides for that purpose because I do not have experience in scrapie diagnosis and would not consider my observations meaningful.

 

I appreciated the additional information about the original study done by Dr. Doi. Although I've heard bits and pieces of the story from different people, this was the first time I had heard that 60 of the pigs were diagnosed as having encephalitis or meningitis. I think that fact, plus the fact that the pigs were only about 6 months old, should certainly indicate that it's highly unlikey that a spongiform encephalopathy epidemic was causing the CNS signs observed. Whether the 1 pig with the questionable encephalopathy lesions was a TSE could be debated, I suppose. The age would seem to argue against it and the immunohistochemistry result would also (at least that's my opinion).

 

We disagree about the implications of age regarding the liklihood of TSE in a 6-month old pig. Certainly dose has an effect on incubation period in experimental transmissions and probably also in the "natural" acquired transmissions. However, regardless of the manner of transmission, I don't know of any first passage experimental interspecies transmission where the incubation period was as short as 6 months.

 

Early onset in mice were achieved only after adaptation through at least 1 intraspecies transfer. I believe the same is true for development of the hamster models. With regard to acquired transmissions, Linda Detwiler's review on scrapie cites research that indicated infectivity was found in CNS tissues of lambs as early as 4 months of age: however, they were not showing clinical signs. From what I can find in the literature, a clinical case of scrapie under 2 years of age would be exceptional, but with the amount of material published on that disease I wouldn't want to say it hasn't happened.

 

With TME the shortest incubation I've seen reported was 9 months. Elizabeth Williams has indicated that the youngest case of CWD observed in their wildlife facilities was 18 months old. You stated that in England calves were getting BSE by one year. In the experimental BSE transmissions cattle didn't develop clinical signs until the second year of observation and the earlest sign we observed in cattle inoculated with sheep scrapie was 14 months.

 

With respect to swine, the only model we have is the experimental transmission of BSE. The animal first developed signs about 17 months after inoculation. I think that it would be highly unlikely for a 6 month old pig to be showing CLINICAL signs of a TSE (the claim in this particular situation). One can never say never but it seems reasonable to at least examine what is known and make an educated estimate about what is likely.

 

A case-control study of CJD. Dietary risk factors. Am J Epidemiol 122 (3): 443-451 (1985) Davanipour Z, Alter M, Sobel E, Asher DM, Gajdusek DC The mode of natural transmission of Creutzfeldt-Jakob disease remains unknown. In a case-control study conducted in 1981-1983 to evaluate possible dietary and other sources of the disease, 26 cases were ascertained in the mid-Atlantic region of the United States, 23 of which were obtained from accumulated records of the Laboratory of Central Nervous System Studies of the National Institutes of Health. Controls included 18 family members and 22 hospital-matched individuals (total sample size, 66). An increased consumption among patients was found for roast pork, ham, hot dogs (p less than 0.05), roast lamb, pork chops, smoked pork, and scrapple (p less than 0.1). An excess consumption of rare meat (p less than 0.01) and raw oysters/clams (p less than 0.1) was also reported among the patients. Liver consumption, among organ foods, was greater (p less than 0.1) among the cases. If Creutzfeldt-Jakob disease is acquired through ingestion of foods containing the agent, then the food items identified may be among those which need to be evaluated more intensively. Larger case-control studies with more focused dietary questions are warranted.

 

Sundlof can't comment From: Dr. Stephen Sundlof D.V.M., Ph.D. Director, Center for Veterinary Medicine Food and Drug Administration :

 

At the present time FDA is in the process of developing a final rule which will regulate the feeding of certain animal-derived protein to other animals. In addition to studying the scientific literature pertaining to TSE's, we have received 700 comments relating the proposed rule that was published in the Federal Register on January 3, 1977. The information provided by Dr. Hansen and others will be considered in developing the final rule along with all of the other information and comments that have been officially submitted to FDA. Until the final rule is published, FDA is prohibited from commenting on information that might impact the final rule. Therefore, I am unable to respond to the documents in Dr. Hansen's letter.

 

I do not have access to the photomicrographs of the histopathology slides, and I was unaware of their existance until Dr. Hansen brought the issue to my attention. Furthermore, I do not have addresses or telephone numbers for Drs. Doi. Langheinrich, or Hadlow. Someone from the USDA would have this information but I am not sure who that would be.

 

Webmaster had written: " Do photomicrographs of any of the 12 slides exist? If you have any of them, I would like to scan a few of these and post them at high resolution on the internet so that pathologists world-wide could view and comment on them.

 

Primary parenteral transmission of bovine spongiform encephalopathy to the pig. Veterinary Record 1990 127 13 338 Dawson, M.; Wells, G. A. H.; Parker, B. N. J.; Scott, A. C. Ten, weaned one- to two-week old piglets from a specific pathogen free breeding herd were inoculated under halothane anaesthesia by simultaneous injections intracerebrally (0.5 ml) intravenously (1 to 2 ml) and intraperitoneally (8 to 9 ml) with an inoculum consisting of 10% saline suspension of pooled homogenised brainstem from 4 natural bovine spongiform encephalopathy cases. Control piglets were similarly inoculated with saline. After 69 weeks one challenged pig showed mild aggressive behaviour towards the animal attendants. Intermittent inappetence and depression were also noted. Within one week the behavioural changes included aimless biting activity and there was mild symmetrical ataxia. The ataxia progressed and 5 weeks after onset of signs the gait ataxia was generalised with hypermetria and wide-based stance. At this time the pig was killed. Histopathological examination of the brain revealed spongiosis of grey matter neuropil with greatest intensity in the medial geniculate body, superior colliculus and corpus striatum. There was sparse vacuolation of neuronal perikarya in the dorsal nucleus of the vagina nerve and widespread astrocytic reaction. Characteristic fibrils associated with transmissible spongiform encephalopathies were detected by electron microscopy.

 

One good question is what _pooled_ medical products do they make from pigs. The key issues for spread of this disease are the amplification cycle and distribution pooling. That is, one rotten apple by itself is less of a problem than if it is in a barrel. – webmaster

 


 

IN CONFIDENCE

 

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY 1. CMO should be aware that a pig inoculated experimentally (ic, iv, and ip) with BSE brain suspension has after 15 months developed an illness, now confirmed as a spongiform encephalopathy. This is the first ever description of such a disease in a pig, although it seems there ar no previous attempts at experimental inoculation with animal material. The Southwood group had thought igs would not be susceptible. Most pigs are slaughtered when a few weeks old but there have been no reports of relevant neurological illness in breeding sows or other elderly pigs.

 

...see full text ;

 


 

IN CONFIDENCE

 

So it is plausible pigs could be preclinically affected with BSE but since so few are allowed to reach adulthood this has not been recognised through clinical disease. ...

 


 

snip...

 

CONFIDENTIAL EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

 

PLEASE NOTE, these old BSE Inquiry links take a while to open with the wayback machine, so be patient. ...tss Title: Experimental Intracerebral and Oral Inoculation of Scrapie to Swine: Preliminary Report In the United States, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine and poultry still occurs. The potential for swine to have access to scrapie-contaminated feedstuffs exists, but the potential for swine to serve as a host for replication/accumulation of the agent of scrapie is unknown. The purpose of this study was to perform oral and intracerebral inoculation of the U.S. scrapie agent to determine the potential of swine as a host for the scrapie agent and their clinical susceptibility. snip... IN CONFIDENCE EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY 1. CMO should be aware that a pig inoculated experimentally (ic, iv, and ip) with BSE brain suspension has after 15 months developed an illness, now confirmed as a spongiform encephalopathy. This is the first ever description of such a disease in a pig, although it seems there ar no previous attempts at experimental inoculation with animal material. The Southwood group had thought igs would not be susceptible. Most pigs are slaughtered when a few weeks old but there have been no reports of relevant neurological illness in breeding sows or other elderly pigs. ...see full text ;

 


 

we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.

 


 

May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...

 


 

3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...

 


 

But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...

 


 

Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....

 


 

snip...

 

It was not until . . . August 1990, that the result from the pig persuaded both SEAC and us to change our view and to take out of pig rations any residual infectivity that might have arisen from the SBOs.

 


 

4.303 The minutes of the meeting record that: It was very difficult to draw conclusions from one experimental result for what may happen in the field. However it would be prudent to exclude specified bovine offals from the pig diet. Although any relationship between BSE and the finding of a spongiform encephalopathy in cats had yet to be demonstrated, the fact that this had occurred suggested that a cautious view should be taken of those species which might be susceptible. The 'specified offals' of bovines should therefore be excluded from the feed of all species. 17

 


 

7 OF 10 LITTLE PIGGIES WENT ON TO DEVELOP BSE;

 

1: J Comp Pathol. 2000 Feb-Apr; 122(2-3): 131-43. Related Articles, Links Click here to read

 

The neuropathology of experimental bovine spongiform encephalopathy in the pig.

 

Ryder SJ, Hawkins SA, Dawson M, Wells GA. Veterinary Laboratories Agency Weybridge, Woodham Lane, New Haw, Addlestone, Surrey, KT15 3NB, UK.

 

In an experimental study of the transmissibility of BSE to the pig, seven of 10 pigs, infected at 1-2 weeks of age by multiple-route parenteral inoculation with a homogenate of bovine brain from natural BSE cases developed lesions typical of spongiform encephalopathy. The lesions consisted principally of severe neuropil vacuolation affecting most areas of the brain, but mainly the forebrain. In addition, some vacuolar change was identified in the rostral colliculi and hypothalamic areas of normal control pigs. PrP accumulations were detected immunocytochemically in the brains of BSE-infected animals. PrP accumulation was sparse in many areas and its density was not obviously related to the degree of vacuolation. The patterns of PrP immunolabelling in control pigs differed strikingly from those in the infected animals. PMID: 10684682 [PubMed - indexed for MEDLINE]

 


 

Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie.

 

Emerg Infect Dis. 2009 Aug; [Epub ahead of print]

 


 

Wednesday, July 06, 2011

 

Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation snip... In the US, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine, mink and poultry still occurs. Although unlikely, the potential for swine to have access to TSE-contaminated feedstuffs exists.

 

snip...

 


 

Wednesday, July 06, 2011

 

Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation (see tonnage of mad cow feed in commerce USA...tss)

 


 

In an experimental study of the transmissibility of BSE to the pig, seven of 10 pigs, infected at 1-2 weeks of age by multiple-route parenteral inoculation with a homogenate of bovine brain from natural BSE cases developed lesions typical of spongiform encephalopathy.

 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=10684682&dopt=Abstract Title: Experimental Intracerebral and Oral Inoculation of Scrapie to Swine: Preliminary Report

 

In the United States, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine and poultry still occurs. The potential for swine to have access to scrapie-contaminated feedstuffs exists, but the potential for swine to serve as a host for replication/accumulation of the agent of scrapie is unknown. The purpose of this study was to perform oral and intracerebral inoculation of the U.S. scrapie agent to determine the potential of swine as a host for the scrapie agent and their clinical susceptibility. snip... snip... In the United States, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine and poultry still occurs. The potential for swine to have access to scrapie-contaminated feedstuffs exists, but the potential for swine to serve as a host for replication/accumulation of the agent of scrapie is unknown. The purpose of this study was to perform oral and intracerebral inoculation of the U.S. scrapie agent to determine the potential of swine as a host for the scrapie agent and their clinical susceptibility.

 

see full text and more transmission studies here ;

 


 

 snip... see full text ;

 

Thursday, November 10, 2011

 

National Meat Association v. Harris Docket No., 10-224 DEADSTOCK DOWNER PIGS AND PORCINE SPONGIFORM ENCEPHALOPATHY PSE Court Likely to Overturn Calif. Law on Livestock

 


 

 Friday, April 20, 2012

 

Ultrastructural findings in pigs experimentally infected with bovine spongiform encephalopathy agent

 


 

Wednesday, July 29, 2015

 

Porcine Prion Protein Amyloid or mad pig disease PSE

 


 

Monday, August 10, 2015

 

Detection and Quantification of beta-Amyloid, Pyroglutamyl A beta, and Tau in Aged Canines

 


 

Friday, August 7, 2015

 

Transgenic Mouse Bioassay: Evidence That Rabbits Are Susceptible to a Variety of Prion Isolates

 


 

PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS

 

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

 

O18

 

Zoonotic Potential of CWD Prions

 

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

 

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

 

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

 

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

 

Additionally, human rPrP was competent for conversion by CWD and fCWD.

 

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

 


 

From: Terry S. Singeltary Sr.

 

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

 

To: Terry S. Singeltary Sr.

 

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

 

THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE

 

R. G. WILL

 

1984

 

*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). (SEE LINK IN REPORT HERE...TSS) PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;

 

snip...

 


 

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***

 


 

*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.

 


 

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations

 

Emmanuel Comoy, Jacqueline Mikol, Val erie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France

 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. *** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, ***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold longe incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), ***is the third potentially zoonotic PD (with BSE and L-type BSE), ***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.

 

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

 

***thus questioning the origin of human sporadic cases...TSS

 

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

 


 

O35

 

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

 

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

 

E-mail: jacqueline.mikol@wanadoo.fr

 

Uncommon prion disease induced in macaque ten years after scrapie inoculation

 

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

 

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

 

Results: The three elements of the triad were present:

 

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

 

The notable data were the following

 

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

 

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

 

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

 

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

 

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

 


 

Tuesday, December 16, 2014

 

Evidence for zoonotic potential of ovine scrapie prions

 

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

 

Abstract

 

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

 

Subject terms: Biological sciences• Medical research At a glance

 


 

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

 

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

 

snip...

 

R. BRADLEY

 


 

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

 

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

 

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

 

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

 

snip...

 

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

 

PMID: 6997404

 


 

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

 

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

 

snip...

 

76/10.12/4.6

 


 

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

 

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

 

Gibbs CJ Jr, Gajdusek DC.

 

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

 

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

 

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

 

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

 

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

 


 


 


 


 

Friday, January 30, 2015

 

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

 


 

Thursday, March 26, 2015

 

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

 


 

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

 

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

 

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

 

Chris Plinston, Patricia Hart, Angela Chong, Nora Hunter, James Foster, Pedro Piccardo, Jean C. Manson, and Rona M Barron* Neuropathogenesis Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin, Midlothian, UK; Laboratory of Bacterial and TSE Agents, Food and Drug Administration, Rockville, MD, USA

 

* To whom correspondence should be addressed. Email: rona.barron@roslin.ed.ac.uk .

 

Abstract

 

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

 


 


 

BSE: TIME TO TAKE H.B. PARRY SERIOUSLY

 

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

 


 

Tuesday, August 4, 2015

 

FDA U.S. Measures to Protect Against BSE

 


 

 

Terry S. Singeltary Sr.

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