Scrapie TSE Prion United States of America a Review February 2021 Singeltary et al
Scrapie TSE Prion United States of America a Review February 2021 Singeltary et al
Tue, Feb 2, 2021 4:40 pm
Scrapie TSE Prion United States of America a Review February 2021 Singeltary et al
SCRAPIE USA MAP 1947 1977 MAP
Epidemiology of Scrapie in the United States 1977
Slow Transmissible Diseases of the Nervous System: Volume 1
EPIDEMIOLOGY OF SCRAPIE IN THE UNITED STATES
James Hourrigan1, Albert Klingsporn2, W. W. Clark3, and M. de Camp4
United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services
ABSTRACT Observations and experiences with scrapie in the United States during the past 25 years have consistently shown it was a disease that spreads from flock to flock, state to state, or from country to country by movement of infected, but apparently normal sheep which were incubating the disease but had not yet reached the age of clinical manifestation. The disease progressed relentlessly until the animal reached the age of manifestation, irrespective of whether the animal remained in the parent flock or had been moved to another flock, state, or country.
The means of spread from animal to animal was more difficult to explain. A close study of parent-progeny relationships suggested that maternal transmission played a dominant role and that there is an inherited component in the level of incidence. When previously unexposed Angora or dairy goats or sheep of the Suffolk, Hampshire, Rambouillet, or Targhee breeds were placed in contact with natural cases of scrapie, and subsequently bred within their own groups, scrapie developed in a few of the sheep first exposed at 3 to 9 months of age and in 14 to 39% of the sheep progeny, born and reared in the infected environment. Scrapie occurred in the progeny of all breeds of goats so exposed. The incidence in Angora goat progeny was 26% and in dairy goat progeny 61%. Dairy goats removed from scrapie exposure at 6 months of age or older developed scrapie, however, those removed at birth did not. Sheep removed from exposure at birth or at 4, 9, or 20 months of age developed scrapie. There was a progressive increase in scrapie incidence among those removed at older ages.
1Federal Center Building, Hyattsville, Maryland
2Federal Center Building, Hyattsville, Maryland
3Scrapie Field Trial, Mission, Texas
4Scrapie Field Trial, Mission, Texas
INTRODUCTION’
Scrapie is a naturally occurring, fatal disease of sheep and goats caused by a filterable, transmissible, self-replicating agent considered by some workers to be a small virus. The virus is unusually resistant to heat and other physical and chemical abuse, including formaldehyde, and to ultraviolet and ionizing radiation. The early signs of natural scrapie are usually subtle changes in behavior or temperament followed by more obvious clinical signs which are progressive and include pruritus, debilitation, rubbing against fixed objects often accompanied by rapid movements of the tongue and lips, grinding of teeth, biting of feet and limbs, locomotor incoordination and, usually, loss of wool, condition, and weight. The course of the clinical disease varies from 1 to 8 months, but may be much longer. Suspicious signs, which on rare occasions persisted or recurred over a period of more than 2 years, were seen. Recovery in an obvious clinical case was not observed. In Icelandic sheep, the signs were primarily those of incoordination of gait without prominent pruritus, Palsson and Sigurdsson, 1958 (1). Recently, pruritus was more evident, Palsson, Personal Communications, 1978. In northern India, sheep showed a severe pruritus but not a protracted period of locomotor incoordination, Zlotnik and Katiyar, 1961 (2). In Suffolk sheep in Britain, there was usually both pruritus and incoordination; however, either could be absent, and extensive neurological lesions could be present in the absence of unequivocal signs of both, Dickinson et al., 1965 (3).
Fig. 1 showed the countries in which scrapie has been reported. The disease was recognized in England, Scotland, Wales, and continental Europe, including Germany, France, and Spain, about 250 years ago and has been reported there in many breeds of sheep. In Iceland, scraple is called rida, Sigurdsson, 1954 (4). Reports of scrapie outbreaks in other countries, largely due to the importation of sheep from Britain, included those in New Zealand, Brash, 1952 (5), and Brash, 1952 (6); Australia, Bull and Murnane, 1958 (7); India, Zlotnik and Katiyar, 1961 (2); Hungary, Aldasy and Suveges, 1964 (8); the Netherlands, Van der Akker et al., 1968 (9); Bulgaria, Ivanov and Haralambiev, 1970 (10); Belgium, Hoorens and Oyaert, 1966 (11); Republic of South Africa, Van der Merwe, 1966 (12); and Kenya, Cooper, 1973 (13). Outbreaks have also occurred in The Federal’ Republic of Germany (West), Von Hiepe et al., 1973 (14); Isle of Man, Italy, Lebanon, Somalia, United Arab Emirates, Yemen, Norway, Ireland, Northern Ireland, and Colombia, South America (FAO-WHO-OIE, 1975, 1976, and 1977, Annual Health Yearbook) and in Austria and former East Prussia.
In the Western Hemisphere, scrapie was first reported in Canada in 1938, Schofield, 1938 (15), and in the United States in Michigan, in 1947, Thorp et al., 1952 (16). The basic source of scrapie in these countries was also British sheep. More extensive outbreaks were disclosed in the United States, in 1952, in California, Stuart et al., 1952 (17), and Ohio, Wagner et al., 1954 (18).
Scrapie has now been reported in the United States in 203 Suffolk flocks, 10 Cheviot flocks, 3 Hampshire flocks, 2 Montadale flocks, and 1 mixed breed flock, Klingsporn and Hourrigan, 1978 (19).
The States and counties involved in scrapie outbreaks were shown in Fig. 2. Although the 219 outbreaks were widespread geographically with 31 States involved, it was encouraging to note that the eradication program restricted further spread. For example, California had 13 outbreaks, but none since 1969. Indiana had 28 outbreaks but none since 1973, and Ohio with a total of 13 outbreaks had reported none since 1966.
Fig. 3 illustrated the spread of scrapie through the movement of sheep incubating the disease. In this particular Situation the disease became entrenched in particular flocks and spread to many other flocks in other States. In a typical situation, the disease became established, most often in purebred flocks, and spread by sheep sold at 2 or 3 or fewer years of age. When the index case was disclosed, all possibly-exposed sheep were traced often disclosing additional scrapied animals in other receiving flocks. Although there was substantial circumstantial evidence against certain suspected source flocks, it was often difficult to prove the disease was present in such flocks. This could have been because sheep were usually sold prior to the age of manifestation or perhaps the owners innocently or deliberately failed to report suspect cases for fear of jeopardizing customary markets.
Evidence of natural scrapie in goats is accumulating. The disease was reported in 1942 in a goat reared with a flock of scrapied sheep in France, Chellé, 1942 (20). In Scotland, 4 of 6 dairy goats maintained in a stall, in contact from the time they were less than 1 week old with a succession of natural cases (mainly Suffolks), developed scrapie at 39, 39, 39, and 47 months of age. In a second similar experiment, 55% of 11 exposed goats developed serapie at 29, 32, 32, 32, 36, and 37 months of age, Brotherston et al., 1968 (21).
Three goats developed scrapie when held in contact from 1 day of age with scrapled sheep for 40 months, Stamp, 1962 (22).
Scrapie was diagnosed in a 5-year-old goat reared in a scrapied flock of Suffolk sheep in Missouri, Hourrigan et al., 1969 (23). In Canada, scrapie was diagnosed in a 7- or 8-year-old goat born in a flock where scrapie had occurred in sheep, Stemshorn, 1975 (24). In Britain, scrapie was reported in a 4-year-old and an 8-year-old Saanan goat which had very little contact with any sheep, Harcourt and Anderson, 1974 (25). Scrapie was diagnosed in an uninoculated control adult goat purchased at 3 years of age from a dealer, MacKay and Smith, 1961 (26).
Indirect transmission of natural scrapie to 10 of 25 test sheep following exposure on a rotational basis to pastures used by scrapied sheep was reported, Greig, 1940 (27).
Following exposure indoors to a succession of naturally scrapied sheep, 43% of 7 Scottish Blackface lambs, developed scrapie at 42 to 44 months of age, Brotherston et.al., 1968 (21).
Scrapie occurred in 28% of purebred Scottish Blackface sheep due to lateral transmission under lifetime contact, Dickinson et al., 1974 (28).
METHODS
A Scrapie Field Trial was developed at Mission, Texas, to provide additional information for the eradication program on the epidemiology of natural scrapie. The Mission Field Trial Station is located on 450 acres of pastureland, part of the former Moore Air Force Base, near Mission, Texas. It was designed to bring previously exposed, and later also unexposed, sheep or goats to the Station and maintain and breed them under close observation for extended periods to determine which animals would develop scrapie and define more closely the natural spread and other epidemiological aspects of the disease.
The 547 previously exposed sheep brought to the Mission Station beginning in 1964 were of the Cheviot, Hampshire, Montadale, or Suffolk breeds. They were purchased as field outbreaks occurred, and represented 21 bloodlines in which scrapie had been diagnosed. Upon arrival at the Station, the sheep were maintained on pasture, with supplemental feeding as necessary. The station was divided into 2 areas: (1) a series of pastures and-pens occupied by male animals only, and (2) a series of pastures and pens occupied by females and young progeny of both sexes. Lambing and kidding occurred in the female area, with lambs remaining with the dams until weaning. At weaning, young males were removed to the male area, and females were temporarily separated from their dams, but remained in the female area. (?) weaning, males and females were kept separated and not allowed to mix or use the same pastures or facilities, except for those males which were chosen for breeding and taken temporarily to the breeding pens. To study familial relationships of the disease, a particular ram was bred to a selected ewe and re- bred to the same ewe in succeeding years to produce as many full sibs as possible.
Numbered duplicate ear tags were placed in both ears of each animal. Sheep were also wool-branded with a number, corresponding to the ear tag number, and rebranded after each semiannual shearing.
Prior to the arrival of exposed sheep, in November 1964, the premises were considered free of contamination by scrapie virus. No livestock had occupied the pastures since 1942, when the Air Base had been established.
Previously unexposed animals were also taken to the Station beginning in 1965 and were placed in direct contact with the infected flock, The previously unexposed animals included 11 Angora goats, 6 Nubian or Toggenburg dairy goats, and 31 Rambouillet, 31 Targhee, 33 Hampshire, and 28 Suffolk sheep. These animals were carefully selected to assure freedom from previous exposure to scrapie. No field cases of scrapie have been found in Rambouillet or Targhee sheep or Angora goats in the United States. Only 1 field case has been reported in a dairy goat, Hourrigan et al., 1969 (23), and 3 field cases in Hampshire sheep. These 4 cases had been raised in flocks containing Suffolk sheep. Twenty of the Suffolks were imported from New Zealand, which had been scrapie-free for more than 20 years.
Later, certain sheep or goats born at the Station were removed from exposure at birth and at 4, 6, 9, or 20 months of age and placed in isolation pens at the Station for long term observation.
Scrapie incidence (percentage of scrapie) was calculated by dividing the number of scrapied animals by the number of animals at risk. Animals were not diagnosed as scrapied unless confirmed by histological examination, McDaniel et al., 1966 (29) and/or by inoculation into mice.
To be considered at risk and scrapie-free, animals had to have reached at Least 24 months of age, and if they had died, high quality brain tissue was submitted to the laboratory and found to be histologically negative for scrapie. Animals brought to the Station and still alive had to reach at least 100 months of age and those born at the Station 60 months of age to be considered at risk and scrapie free.
The age (months) of scrapied animals at death or sacrifice was used as “age scrapied" in all calculations. Animals of doubtful category (clinically : -cious, histologically inconclusive, or showing post-mortem autolytic brain damage were not considered at risk insofar as these calculations were concerned.
RESULTS
Table 1 indicated that previously exposed sheep brought to the Station at various times and ages (1 to 89 months old) included 333 Suffolks at risk. Of these, 98 (29%) developed scrapie. This demonstrated the necessity to slaughter such sheep to prevent further Spread of the disease, These previously exposed Suffolks were bred at the Station and produced 446 progeny at risk. Of these 153 (34%) developed scrapie.
Although the minimum and average ages when scrapied were similar for both groups, some of the previously exposed Suffolks brought to the Station developed scrapie when much older--ewes 60 to 142 months old and rams 67 to 102 months old. Of the 153 Suffolks born at the Station, only 3 were more than 60 months of age (65, 66, and 69 months old).
This difference in age scrapied was attributed to the fact that the Suffolks born at the Station may have been subject to a greater exposure from birth.
It was also observed that when both dam and progeny were scrapied, the progeny nearly always developed clinical disease at a younger age than their respective dam. Thirty-two dams were scrapied at an average of 60 months of age. Forty-six of their progeny developed the disease at an average of 38 months (range 25 to 53 months). Thirty-seven of the 46 progeny were younger than the dam (average 20 months younger, range 2 to 99 months younger). Two were scrapied at the same age as their dams, and 8 were older (average 5 months, range 1 to 13 months older).
Although the incidence of scrapie was considerably Greater in the progeny of scrapied compared to free dams, the progeny of either scrapied or free dams manifested scrapie at the typical age and irrespective of the age their respective dams were scrapied. The differences in ages that dams and progeny were scrapied was believed due to difference of exposure, particularly whether they were exposed at an early age,
Table 2 summarized the data on exposed Suffolks and was Prepared so as to show scrapie incidence in the progeny of dams and sires of known Scrapie status. The scrapie incidence in the progeny of Free X Free parents was 25%, progeny of scrapied Sires 39%, and scrapied dams 42%. When both sire and dam were scrapied, the scrapie incidence in 18 Progeny at risk was 78%,
When the scrapie status of the sire was ignored, scrapie incidence in the progeny of free dams was 34% and in pre y of scrapied da as 62%. When the scrapie status of the dam was ignored, scrapie incidence in the progeny of free sires was 26% and in the progeny of scrapied sires was 45%.
Although the scrapie incidence was nearly double in the progeny of scrapied compared to free dams, the latter con- tributed a greater number of scrapied progeny, 116, compared to only 51 cases which had scrapied dams. This was because free dams made a considerably heavier contribution to the progeny at risk4-342 compared to 82. It was felt that in farm flocks a similar situation could exist.
It was possible that free dams could have been misclassified; however, this was unlikely to have been significant, unless "nonclinical or carrier" dams exist. In this Suffolk group, the ages of 100 free dams of scrapied progeny ranged from 25 to 160 (average 97) months. These free dams did not show clinical signs of scrapie, and there were no histopathological lesions suggesting scrapie in those which died. If one cannot classify as free, ewes which have reached 97 months (average) and did not develop the disease, from a practical standpoint, it is not possible to classify sheep as free, at least on the basis of clinical signs and histology. The free dams of 50% of the scrapied progeny were more than 100 months of age, averaging 126 months.
Upon arrival at the Mission Station at 3 to 9 months of age, the 140 previously unexposed sheep and goats were placed in infected pastures and corrals and were subjected to contact with a succession of natural cases of scrapie in sheep, and eventually also in goats. These animals were bred only within their respective groups and were not crossbred to other breeds of sheep or those brought to the Station from infected flocks or their progeny. The male or female animals mixed freely with animals of their respective sex of the infected Flock and were similarly identified and subjected to similar flock management and diagnostic procedures.
Table 3 indicated that natural scrapie had occurred in 5 of the 140 previously unexposed sheep. One case each occurred in Rambouillet, Targhee, and Hampshire ewes at 88, 89, and 89 months of age and in 2 Suffolk ewes at 73 and 102 months of age, and 85, 82, 80, 64, and 93 months following initial natural exposure. This represented a natural situation involving lateral spread, under the circumstances involved, when sheep were not exposed when very young. Scrapie was not detected clinically or histologically in any of the dairy or Angora goats brought to the Station. The disease occurred in an average of 27% of the progeny of previously unexposed sheep or goats born at the Station and included cases in progeny of all breeds of sheep or goats taken there, The incidence in the progeny ranged from 14% in Rambouillet sheep to 61% in dairy goats.
These data showed that scrapie spread laterally, by contact exposure, from scrapied te previously free animals, but at an apparently lower rate when exposure was first received at the age of 3 te 9 months. These animals were presumed to be susceptible to the disease, as their progeny developed scrapie at rates and ages similar (on the average) to the progeny, pf previously exposed Suffolk sheep born and reared in the same environment.
It was suggested that the progeny of previously unexposed animals developed scrapie at a much higher rate than their parents, and at a younger age, because they were subjected to exposure from birth. The data did not rule out the possibility that the animals born at the Station could have also received the virus from their dams "vertically" prior to, at, or following birth.
Table 4 summarized the scrapie incidence in the progeny, born at the Station, of previously unexposed dairy goats. The data were prepared so as to show scrapie incidence in the progeny of dams and sires of known scrapie status.
The 58% incidence in the progeny (24 at risk) of Free X Free parents was more than twice the 25% seen in the Suffolk group (Table 2). Scrapied sires did not increase the incidence in goat progeny (it was 44%); scrapied dams increased the incidence to 71%. When both sire and dam were scrapied the incidence was 89%, with only 9 goat progeny at risk.
When the scrapie status of the sire was ignored, the scrapie incidence in the progeny of free dams was 56% and in the progeny of scrapied dams it was 74%.
Free dams contributed 34 progeny at risk and scrapied dams 31 progeny.
When the scrapie status of the dam was ignored, scrapie incidence was 64% in the progeny of free sires and a similar 66% in the progeny of scrapied sires.
A total of 244 sheep (127 Suffolk, 59 Rambouillet, and 58 Targhee) were removed from scrapie exposure within a few hours of birth or at 4, 9, or 20 months of age and placed in isolation pens. Removal of sheep from exposure at these ages was selected as being representative of usual flock operations when sheep might be sold from an infected flock at weaning, the first fall or the second fall after their birth.
Table 5 reflected the fate of such animals. Four of the 6 scrapied sheep which had been isolated at birth were Suffolks and the 2 older animals were Targhees. The first case in the group isolated at birth was a Targhee, progeny of a ewe that did not develop clinical scrapie. The scrapie incidence in 36 at risk Suffolks removed from exposure at birth was 11%, considerably less then that expected had these animals remained in an infected environment.
Table 6 reflected the status of 51 goats isolated from scrapie exposure at birth, and at 6, 8 to 10, 20, 32 to 59 and 60 to 82 months of age.
None of the goats removed at birth developed scrapie, although all 5 of those alive at 5 years of age had scrapied dams and 1 also had a scrapied sire. The sire of the remaining 4 had sired 7 scrapied progeny. Under such circumstances, had they remained in an infected environment nearly all of these goats would have been expected to develop scrapie. With the exception of the 20 month group, scrapie occurred at an incidence of 25 to 100% in all other groups and at the expected age. A further observation was that 4 of the progeny of these dairy goats, born and kept apart from any sheep, developed scrapie which suggested that goats were not "dead- end hosts" insofar as scrapie was concerned.
Table 7 recorded the fate of progeny of certatn selected scrapied or free Suffolk sheep or dairy goat dams.
Suffolk ewe G298 was scrapied at 46 months of age. She had twin lambs in 1969 and 1 lamb in 1970. All 3 lambs developed scrapie. Suffolk ewe G27a was scrapied at 39 months. Her lamb born in 1966 was serapied at 53 months; however, her lambs born in 1967 and 1968 remained free--l*lived to 102 months of age.
Suffolk ewe G25a died at 131] months of age and was negative clinically and histologically. Mice remained negative following intracerebral inoculation of brain, spleen, and lymph nodes from this ewe. This ewe had 9 progeny at risk, of which 4 developed scrapie and 5 did not. There was no discernible pattern to the cases. In two instances, 1 twin was scrapied and 1 remained free.
Goat B259 was scrapied when 43 months old. All of her 6 progeny at risk developed scrapie.
Goat B14a remained free and died at 101 months of age. Of her 11 progeny at risk, 7 were scrapied and 4 were not.
It was observed at the Station that when scrapied dams had several progeny at risk, 1 or more progeny usually developed the disease. However, many such scrapied dams also had progeny which lived, or are living, considerably beyond the age of their dams and beyond the age animals born at the Station manifested the disease.
It was also observed that individual free dams had free progeny in earlier years followed by scrapied progeny when they were older, or had scrapied progeny when young followed by free progeny when older, or scrapie and free progeny dispersed throughout the dam's breeding life. The same situation occurred in progeny of scrapied dams; however, the pattern was less irregular due to the smaller number of progeny from each scrapied dam and the higher incidence of scrapie in such progeny. circumstances prevented breeding all ewes every year and, thus, many had only 1 progeny at risk. Scrapie developed in 100% of the single progeny at risk of 11 scrapied and 15 free dams. The 26 scrapied progeny were equally divided between ewes and rams.
Table 8 reflected the difference in age scrapied of sheep brought to the Station compared to the age scrapied of those born there. Although the average age of previously exposed sheep (Suffolks) brought to the Station did not differ greatly from the overall average, several animals brought to the Station developed the disease at quite advanced ages. The previously unexposed scrapied animals brought to the Station were also considerably older than animals born there. Progeny of scrapied dams developed the disease at a slightly younger age than did progeny of free dams. The average age was nearly the same for males and females.
DISCUSSION
Observations of natural outbreaks of scrapie indicated that the disease spread from flock to flock by the movement of infected, but apparently normal, sheep which were incubating the disease.
There was no evidence that the disease spread to adjacent flocks in the absence of such movements or that vectors or other host species were involved in the spread of scrapie to sheep or goats; however, these possibilities should be kept open.
In countries where scrapie occurred, it was difficult to know with certainty that sheep or goats were not incubating the disease and would not manifest the disease at some future time. This concept was supported when sheep removed from scrapie exposure at birth, and at 4, 9, or 20 months of age developed scrapie at the expected ages. Thus, sheep born in a contaminated environment had been sufficiently infected so as to develop the disease when they reached the age of manifestation. Unpublished data at the Station demonstrated that scrapie virus could be isolated by intracerebral inoculation of mice from an apparently normal Suffolk sheep as young as 4 months and goats as young as 11 months of age. The dams of both such animals had been scrapied. Attempts to isolate scrapie virus from younger progeny or fetal tissues from scrapied dams had been negative. Histological evidence of natural scrapie in apparently normal sheep had been reported in lambs as young as 11 months, Dickinson et al., 1965 (3). Natural scrapie virus was recovered in Cheviot sheep 8 months old. Renwick and Zlotnik, 1965 (30) claimed to have isolated the agent from apparently normal 4 1/2 month old Bord Leicester lamb ... of a scrapied dam.
Goats removed from exposure at birth had not developed scrapie at 5 years of age, although all had scrapied dams. Had they remained with their dams in the infected environment, nearly all of these 5 goats would have been expected to develop scrapie. However, goats isolated at 6 months of age or older developed scrapie at the expected age. Goats born and kept apart from all sheep, but in contact with scrapied goats, developed scrapie suggesting goats were not dead-end hosts.
When previously unexposed animals 3 to 9 months old were placed on premises where clinical cases were occurring, a small number of such test sheep developed clinical scrapie at rather advanced ages of 73 to 102 months. However, 14 to 61% of the progeny of such sheep or goats developed scrapie at the customary 30 to 60 months of age. This was observed when progeny of previously unexposed Suffolk, Ramboillet, Targhee, or Hampshire sheep or Angora or dairy goats were exposed to scrapied sheep, mainly Suffolks.
Suffolk sheep showed definite familial patterns, suggesting an inherited component and/or maternal transmission of scrapie. Morbidity in the progeny born on infected premises of free sires and free dams was 25% with 105 at risk (58% for dairy goats with 24 at risk) and increased to about 80% or more if both parents were scrapied.
The overall incidence in 283 Suffolk progeny at risk was 36%. Although the incidence was 62% in the progeny of scrapied and 34% in the progeny of free dams, the latter contributed a much greater number of progeny at risk and actually had a larger number of scrapied progeny.
Under similar exposure, the incidence in mixed dairy goats was 61% in 72 progeny at risk. Morbidity was 58% in progeny of free dams and free sires, 44% if the sire only was scrapied, 71% 1f the dam only was scrapied, and 89% if both sire and dam were scrapied.
Limited attempts to isolate scrapie virus from materials which might provide clues for animal to animal spread have been largely negative at the Mission Station. Tissues from scrapied sheep or goats or other materials inoculated intracerebrally or subcutaneously or fed to swiss white outbred mice included feces, urine, saliva, milk, semen, testes, colostrum, and ovary. Mice were also exposed to grass from pastures and manure from sheds believed to be contaminated. Preliminary results were negative. In only 2 instances did inoculated mice develop scrapie, This involved 1 cage of mice inoculated with internal parasites, Haemonchus contortus, and 1 cage of mice inoculated with fetal cotyledon from scrapled goats.
The average age of previously exposed scrapied sheer brought to the ...Station did not differ greatly from the overall average. However, several of these animals showed clinical evidence of the disease at advanced ages, up to 142 months. Previously unexposed animals brought to Mission also developed clinical signs at 73 to 102 months of age, considerably older than their progeny born at Mission.
In the United States, sheep with natural scrapie have on rare occasions shown clinical signs as young as 18 months.of age, Scrapied ewes as old as 142 months and scrapied rams as old as 102 months of age were recorded at the Mission Station; however, the great majority of scrapied sheep and goats were from 30 to 60 months of age. Field cases in younger animals were more likely to be seen when the disease was firmly established in a flock, Clinical natural scrapie was not observed in sheep or goats less than 18 months of age and rarely in animals that young; however, Katiyar, 1962 (31) and Joubert et al., 1972 (32) reported natural scrapie in India and in France in sheep as young as 10 to 12 months of age.
REFERENCES .
snip...
Scrapie Field Trial Experiments Mission, Texas
A Scrapie Field Trial was developed at Mission, Texas, to provide additional information for the eradication program on the epidemiology of natural scrapie. The Mission Field Trial Station is located on 450 acres of pastureland, part of the former Moore Air Force Base, near Mission, Texas. It was designed to bring previously exposed, and later also unexposed, sheep or goats to the Station and maintain and breed them under close observation for extended periods to determine which animals would develop scrapie and define more closely the natural spread and other epidemiological aspects of the disease.
The 547 previously exposed sheep brought to the Mission Station beginning in 1964 were of the Cheviot, Hampshire, Montadale, or Suffolk breeds. They were purchased as field outbreaks occurred, and represented 21 bloodlines in which scrapie had been diagnosed. Upon arrival at the Station, the sheep were maintained on pasture, with supplemental feeding as necessary. The station was divided into 2 areas: (1) a series of pastures and-pens occupied by male animals only, and (2) a series of pastures and pens occupied by females and young progeny of both sexes. ...
snip...see full text ;
Mission, Texas Scrapie transmission to cattle study
Wilbur Clarke (reference the Mission, Texas scrapie transmission transmission to cattle study) is now the State Veterinarian for Montana based at Helena.
I was given confidential access to sections from the Clarke scrapie-cattle transmission experiment. Details of the experimental design were as supplied previously by Dr. Wrathall (copy of relevant information appended). Only 3 animals (2 inoculated with 2nd pass Suffolk scrapie and 1 inoculated with Angora goat passaged scrapie) showed clinical signs. Clinical signs were characterised by weakness, ''a stilted hindlimb gait'', disorientation, ataxia and, terminally, lateral recumbency. The two cattle from which I examined material were inocluated at 8 months of age and developed signs 36 months pi (goat scrapie inoculum) and 49 months pi (one of the Suffolk scrapie inoculated) respectively. This latter animal was killed at 58 months of age and so the clinical duration was only 1 month. The neuropathology was somewhat different from BSE or the Stetsonville TME in cattle. Vacuolar changes were minimal, to the extent that detection REQUIRED CAREFUL SEARCHING. Conversely astrocyte hypertrophy was a widespread and prominent feature. The material requires DETAILED NEUROPATHOLOGICAL ASSESSMENT BUT WHETHER OR NOT THIS WILL BE DONE REMAINS A QUESTION.
Transmission Studies
Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases {the following was written but with a single line marked through it ''first passage (by this route)}...TSS
resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculum (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in ALL of these species with the shortest incubation period in the ferret.
snip...
Appendix 3
VISIT TO USA - DR A E WRATHALL - INFO OH BSE AND SCRAPIE
1. Dr Clark lately of the Scrapie Research Unit, Mission Texas has successfully transmitted ovine and caprine scrapie to cattle. The experimental results have not been published but there are plans to do this. This work was initiated in 1978.
A summary of it is:-
Expt A
6 Her x Jer calves born in 1978 were inoculated as follows with
a 2nd Suffolk scrapie passage:-
i/c 1ml; i/m, 5ml; s/c 5ml; oral 30ml.
1/6 went down after 48 months with a scrapie/BSE-like disease.
Expt B
6 Her or Jer or HxJ calves were inoculated with angora Goat
virus 2/6 went down similarly after 36 months.
Expt C
Mice inoculated from brains of calves/cattle in expts A • B were resistant, only 1/20 going down with scrapie and this was the reason given for not publishing.
Diagnosis in A, B, C was by histopath. No reports on SAT were given.
2. Dr Warren Foote indicated success so far in eliminating scrapie in offspring from experimentally- (and naturally) infected sheep by ET. He had found difficulty in obtaining embryos from naturally infected sheep (cf SPA).
3. Prof. A Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr A Thiermann showed the picture in the "Independent" with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. BSE was not reported in USA.
4. Scrapie incidents (ie affected flocks) have shown a dramatic increase since 1978. In 1953 when the National Control Scheme was started there were 10-14 incidents, in 1978 - 1 and in 1988 so far 60.
5. Scrapie agent was reported to have been isolated from a solitary fetus.
6. A western blotting diagnostic technique (? on PrP) shows some promise.
7. Results of a questionnaire sent to 33 states on the subject of the national sheep scrapie programme survey indicated
17/33 wished to drop it
6/33 wished to develop it
9/13/2005
33
Page 15 of 17
8/33 had few sheep and were neutral
Information obtained from Dr Wrathall's notes of a meeting of the U.S. Animal Health Association at Little Rock, Arkansas Nov. 1988.
end...TSS
NOW, in 1979, it was proven that indeed U.S. scrapie strain that was transmitted to U.S. cattle, did NOT produce a Transmissible Spongiform Encephalopathy (TSE) like the U.K. B.S.E., but a TSE unlike the U.K. B.S.E. SO what does all this tell us? it tells me that there is a possibility that a strain of mad cow disease was circulating in the U.S.A. long, long, before originally thought, only left to be ignored, while incubating and spreading.
3.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE.339 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture.340 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre.341 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle, did not produce the same clinical signs of brain lesions characteristic of BSE.
3.58 There are several possible reasons why the experiment was not performed in the UK. It had been recommended by Sir Richard Southwood (Chairman of the Working Party on Bovine Spongiform Encephalopathy) in his letter to the Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988,342 though it was not specifically recommended in the Working Party Report or indeed in the Tyrrell Committee Report (details of the Southwood Working Party and the Tyrell Committee can be found in vol. 4: The Southwood Working Party, 1988–89 and vol. 11: Scientists after Southwood respectively). The direct inoculation of scrapie into calves was given low priority, because of its high cost and because it was known that it had already taken place in the USA.343 It was also felt that the results of such an experiment would be hard to interpret. While a negative result would be informative, a positive result would need to demonstrate that when scrapie was transmitted to cattle, the disease which developed in cattle was the same as BSE.344 Given the large number of strains of scrapie and the possibility that BSE was one of them, it would be necessary to transmit every scrapie strain to cattle separately, to test the hypothesis properly. Such an experiment would be expensive. Secondly, as measures to control the epidemic took hold, the need for the experiment from the policy viewpoint was not considered so urgent. It was felt that the results would be mainly of academic interest.345
3.59 Nevertheless, from the first demonstration of transmissibility of BSE in 1988, the possibility of differences in the transmission properties of BSE and scrapie was clear. Scrapie was transmissible to hamsters, but by 1988 attempts to transmit BSE to hamsters had failed. Subsequent findings increased that possibility.
337 Fraser, H., Bruce, M., Chree, A., McConnell, I. and Wells, G. (1992) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice, Journal of General Virology, 73, 1891–7; Bruce, M., Chree, A., McConnell, I., Foster, J., Pearson, G. and Fraser, H. (1994) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice: Strain Variation and the Species Barrier, Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 343, 405–11 338 Bruce, M., Will, R., Ironside, J., McConell, I., Drummond, D., Suttie, A., McCordie, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H. and Bostock, C. (1997) Transmissions to Mice Indicate that ‘New Variant’ CJD is Caused by the BSE Agent, Nature, 389, 498–501 339 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606–12 340 YB88/10.00/1.1 341 Cutlip, R., Miller, J., Race, R., Jenny, A., Katz, J., Lehmkuhl, H., Debey, B. and Robinson, M. (1994) Intracerebral Transmission of Scrapie to Cattle, Journal of Infectious Diseases, 169, 814–20 342 YB88/6.21/1.2 343 YB88/11.17/2.4
In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells
3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...
VISIT TO USA - DR AE WRATHALL - INFO ON BSE AND SCRAPIE
1. Dr. Clark lately of the Scrapie Research Unit, Mission Texas has successfully transmitted ovine & caprine Scrapie to cattle. The experimental results have not been published but there are plans to do this. This work was initiated in 1978. A summary of it is;
snip...see handwritten notes from this here;
IN CONFIDENCE
Perceptions of an unconventional slow virus diseases of animals in the U.S.A. G A H Wells
Report of a Visit to the USA April-May 1989
Transmissible Spongiform Encephalopathy
Spongiform Encephalopathy in Captive Wild ZOO BSE INQUIRY
Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME. snip... The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
Scrapie USAHA
Scrapie USA 1997
PROCEEDINGS ONEHUNDREDANDFIRST ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION
October 18-24,1997
8. SCRAPIE: Whereas in 1994 and 1995,102 brains of sheep showing various neuromotor clinical signs had been examined in Israel, all with negative results, one case was confirmed in October 1996. In Norway, since 1991 , the disease has remained confined to Hordaland and Rogaland districts. A new control program was launched in May 1996, which encourages the slaughter of animals having come into contact with infected flocks. In June 1996, scrapie was diagnosed in a sheep on the island of Hokkaido in Japan. This was the first case to be reported in the country since November 1994.
Sheep https://www.usaha.org/upload/Proceedings/2001_ONE_HUNDRED_AND_FIFTH_ANNUA.pdf Dr. John Clifford, USDA APHIS VS, reported on identification in the voluntary scrapie program. EID was not readable 20-30% of the time in some flocks. Tamper resistant eartags bearing premise ID issued by VS is being used in several flocks. VS maintains the database for these premise numbers.
Scrapie USA 2000
PROCEEDINGS ONE HUNDRED AND FOURTH ANNUALMEETING of the UNITED STATESANIMAL HEALTH ASSOCIATION
October 20-27, 2000
On February IO, 2000, there were 48 flocks in the United States listed as infected with scrapie. A national surveillance plan is being developed for scrapie. On December 31,1999, there were 222 pseudorabies infected herds in the country.
Scrapie USA 2001
Scrapie USA 2002
PROCEEDINGS ONE HUNDRED AND SIXTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION
2002
Scrapie Infected and Source Flocks (Dianne Sutton): As of 9/30/02, there was 42 scrapie infected and source flocks. In FY 2002, 94 infected flocks were newly detected and over 259 scrapie cases were confirmed and reported by NVSL. Eighty-six flocks have been released from infected or source status or put on clean-up plans in FY 2002. Five cases of scrapie in goats were reported in FY 2002. During FY 2002, 11,751 animals were tested for scrapie. Laboratory testing has been taking 10 to 11 days on average. During FY 2002, 9.9 million plastic and 6.0 million metal tags were distributed by APHIS.
Scrapie USA 2003
PROCEEDINGS ONE HUNDRED AND SEVENTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION
2003
RESOLUTION NUMBER: 15 APPROVED SOURCE: COMMITTEE ON SHEEP AND GOATS SUBJECT MATTER: SCRAPIE BACKGROUND INFORMATION:
A significant number of sheep in the United States have been identified as immunohistochemistry (IHC) positive on tonsil and/or lymph nodes and IHC negative on obex. This number includes 24% of the sheep that tested positive on one or more tissues as part of Regulatory Slaughter Surveillance. This makes it important that IHC testing on tonsil and lymph nodes be approved as an official test. The United States Department of Agriculture (USDA), Agricultural Research Service (ARS) and Animal and Plant Health Inspection Service (APHIS), Veterinary Services (VS) have compiled data on 2,523 sheep of which 467 were positive on at least one tissue and for which results were available for obex or third eyelid and for tonsil or lymph node. The Kappa analysis showed the concordance between the currently approved tests and lymphoid nodes or tonsil to be 0.91 in the test validation data set and 0.93 for the National Veterinary Services Laboratory (NVSL) data set. As would be expected based on pathogenesis studies, the discrepant positive lymphoid tests were most often seen in young animals. The scientific literature supports the correlation between the detection of PrPsc and the presence of infectivity.
RESOLUTION:
The United States Animal Health Association (USAHA) recommends that the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), Veterinary Services (VS) to approve immunohistochemistry on specific lymphoid tissues as an official test for the determination of a scrapie positive animal in live and dead sheep and goats.
APHIS RESPONSE:
The U.S. Department of Agriculture has approved immunohistochemistry testing on lymph node or tonsil as an official test when conducted at the National Veterinary Services Laboratories or its cooperating laboratories. Animals determined to be lymph node or tonsil
REPORT OF THE COMMITTEE
positive on or after November 7, 2003, at an approved laboratory will be designated scrapie-positive animals.
Infected and Source Flocks
As of September 30, 2003, there were 50 scrapie infected and source flocks (figure 3). There were 73 newly infected flocks reported in FY 2003 (figure 4). In addition, 351 Scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2003 (figure 5). These included 249 regular necropsy cases, 66 validation necropsy
475 SCRAPIE SUB-COMMITTEE REPORT
cases, 32 regulatory third eyelid cases, and 4 validation third eyelid cases. No cases of scrapie in goats were reported in FY 2003. The last case was confirmed in August 2002. New infected and source flocks numbers and the number of these flocks released in FY 2003 are depicted in chart 4. Sixty flocks, or 82 percent of the scrapie infected and source flocks present in FY 2003, were released or put on clean-up plans in FY 2003.
Scrapie: Ovine Slaughter Surveillance (SOSS)
The Center for Epidemiology and Animal Health, has released the first results of the SOSS study. The objective of SOSS was to estimate the national and regional prevalence of Scrapie in mature cull ewes. Prior to the SOSS study, the prevalence of Scrapie in the United States was estimated to be 0.07 percent (based on information from NAHMS Sheep ’96, unpublished data). The SOSS study estimate for the national Scrapie prevalence in mature ewes is 0.20 percent. The prevalence phase of the SOSS study started April 1, 2002, and continued through March 31, 2003. Samples were collected from 12,508 mature sheep at 22 slaughter facilities and a major livestock market during this time period.
The country was divided into four regions: West (CA,OR,WA); Mountain (AZ,CO,ID,MT,NV, NM,OK,TX,UT,WY); Central (IA,KS,MN, MO,NE,ND,SD); and East (AL,AR,CT,DE,FL,GA,KY, IL,IN,LA,MA, ME,MD,MI,MS,NH,NJ,NY,NC,OH,PA,RI,SC,TN,VA,VT,WI,WV). Sheep that could not be traced to a region were grouped as Multi-region. The regions are illustrated in figure 6. The weighted regional prevalence estimates (percent positive) for scrapie in mature sheep are: West = sample size was too small for prevalence estimation - no positives were found in the 670 sheep tested; Mountain = .14%; Central = .21%; East = .52%; and Multi-Region = .13%
Of the 12,508 sheep tested, 34 were found to be scrapie positive of which there were 27 black face, 3 mottled face, 2 white face, and 2 unknown face color. A complete report and analysis will be available in January 2004. Note: The raw prevalence is higher than the weighted prevalence. The difference is the result of weighting each positive based on the number of sheep sampled and the number of sheep killed at each plant.
Regulatory Scrapie Slaughter Surveillance (RSSS)
RSSS started April 1, 2003. RSSS is targeted slaughter surveillance which is designed to identify infected flocks for clean up. Six thousand and six hundred (6600) sheep were sampled during FY 2003, of which test results have been reported for 5,160. There were 17 positive or suspect sheep of which 3 were white face and 14 were black face. Seventeen plants submitted samples.
Scrapie Testing Summary
During FY 2003, 16,803 animals have been sampled or tested for
476
SHEEP AND GOATS
scrapie, which includes: 3,724 regular necropsy cases, 42 third eyelid biopsies for the test validation project, 244 necropsy test validations, 579 third eyelid biopsies for the regulatory program, and approximately 12,214 animals for SOSS and RSSS (chart 5).
Scrapie USA 2004
PROCEEDINGS ONE HUNDRED AND EIGHTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION
2004
There were seventy infected and source flocks identified as of September 30, 2004. In FY2004 a total of 103 new infected and source flocks reported with seventy-seven of those released in FY2004. As of September 30, 2004, 368 scrapie cases had been confirmed and reported by the National Veterinary Services Laboratories (NVSL), of which fifty-four were RSSS cases. One new goat case was reported. Approximately 3,058 animals were indemnified. Dr. Sutton also reported on the Scrapie ovine slaughter surveillance study and the Regulatory Slaughter Surveillance program. Scrapie testing was done on 25,006 animals in FY2004. As of September 30, 2004, 90,322 sheep and goat premises have been assigned identification (ID) numbers in the Scrapie National Generic Database. Official eartags have been issued to 64,040 of the premises.
Scrapie USA 2005
PROCEEDINGS ONE HUNDRED AND NINTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION
2005
For the period of time from January 1, 2005, until October 15, 2005, there were 23 instances of discrepancies in results from 35 flocks. Of those 23 instances, 14 were caused by laboratory error (paperwork or sample mix-up), 3 results from field error, 5 were not completely resolved, and 1 originated from the use of a non-approved laboratory for the first test. As a result of inconsistencies, one laboratory’s certification was revoked by APHIS-VS.
To reduce/eliminate these problems, the Program has placed additional quality requirements on the testing laboratories: additional review of final reports, additional coding systems for testing operations, strict follow-up and reports to NVSL on corrective actions, dual data entry systems, and more frequent inspections.
Infected and Source Flocks
As of September 30, 2005, there were 105 scrapie infected and source flocks. There were a total of 165** new infected and source flocks reported for FY 2005. The total infected and source flocks that have been released in FY 2005 was 128. The ratio of infected and source flocks cleaned up or placed on clean up plans vs. new infected and source flocks discovered in FY 2005 was 1.03 : 1*. In addition 622 scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) in FY 2005, of which 130 were RSSS cases. Fifteen cases of scrapie in goats have been reported since 1990. The last goat case was reported in May 2005. Approximately 5,626 animals were indemnified comprised of 49% non-registered sheep, 45% registered sheep, 1.4% non-registered goats and 4.6% registered goats.
Regulatory Scrapie Slaughter Surveillance (RSSS) RSSS was designed to utilize the findings of the Center for Epidemiology and Animal Health (CEAH) Scrapie: Ovine Slaughter Surveillance (SOSS) study. The results of SOSS can be found at http://www.aphis.usda.gov/vs/ceah/cahm/Sheep/sheep.htm. RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks for clean-up. During FY 2005 collections increased by 32% overall and by 90% for black and mottled faced sheep improving overall program effectiveness and efficiency as demonstrated by the 26% decrease in percent positive black faced sheep compared to FY 2004. Samples have been collected from 62,864 sheep since April 1, 2003, of which results have been reported for 59,105 of which 209 were confirmed positive. During FY 2005, 33,137 samples were collected from 81 plants. There have been 130 NVSL confirmed positive cases (30 collected in FY 2004 and confirmed in FY 2005 and 100 collected and confirmed in FY 2005) in FY 2005. Face colors of these positives were 114 black, 14 mottled, 1 white and 1 unknown. The percent positive by face color is shown in the chart below.
Scrapie Testing
In FY 2005, 35,845 animals have been tested for scrapie: 30,192 RSSS; 4,742 regulatory field cases; 772 regulatory third eyelid biopsies; 10 third eyelid validations; and 129 necropsy validations (Chart 9).
Scrapie USA 2006
PROCEEDINGS ONE HUNDRED AND TENTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION
2006
Infected and Source Flocks
As of September 30, 2006, there were 85 scrapie-infected and source flocks (48 infected and 37 source). There were a total of 116 new infected and source flocks reported for FY 2006. Figure 1 shows the number of new infected and source flocks by year. The total infected and source flock statuses that were released in FY 2006 was 100. A total of 343 positive scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL). Of these, 70 were RSSS cases, (collected in FY 2006 and confirmed in FY 2006 or FY 2007), and 222 positive field necropsy cases (most of these cases were found during depopulations of scrapie exposed animals in infected/source flocks), 14 necropsies of field cases retained long term for test evaluation, and 37 third eyelid regulatory tests confirmed in FY 2006. Three of the field cases were goats. One goat case, in Colorado, could not be linked to exposure in sheep as a result Colorado goats no longer meet the requirements to be classified as lowrisk goats or low-risk commercial goats for interstate movement. Approximately 3,822 animals were indemnified comprised of 62% nonregistered sheep, 30% registered sheep, 5% non-registered goats and 3% registered goats. This represents a 26% decrease over FY 2005 with a significant shift from registered to grade animals.
Regulatory Scrapie Slaughter Surveillance (RSSS) RSSS was designed based on the findings of the Center for Epidemiology and Animal Health (CEAH) Scrapie: Ovine Slaughter Surveillance (SOSS) study. The results of SOSS can be found at http://www.aphis.usda.gov/vs/ ceah/cahm/Sheep/sheep.htm.
RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks for clean-up. During FY 2006, collections increased by 9% overall and by 16% for black and mottled faced sheep compared to FY 2005. Improvement in the overall program effectiveness and efficiency is demonstrated by the 33% decrease in percent positive black-faced sheep compared to FY 2005 (0.67 to 0.45%, based on test results posted before November 6, 2006). During FY 2006, 37,167 samples were collected. The distribution of these samples is shown in figure 2. There have been 70 NVSL confirmed positive cases that were collected in FY 2006. Face colors of these positives were 62 black and eight mottled. The percent positive by face color is shown in the figure 3 below.
Scrapie Testing
In FY 2006, 42,823 animals were sampled for scrapie testing: 37,167 RSSS; 3,649 regulatory field cases, 1,934 regulatory third eyelid biopsies, and 73 necropsy validations.
Scrapie USA 2007
PROCEEDINGS ONE HUNDRED AND ELEVENTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION
2007
Infected and Source Flocks
As of September 30, 2007, there were 37 scrapie infected and source flocks, a decrease of 56 percent from September 30, 2006. There were a total of 72 new infected and source flocks reported for fiscal year (FY) 2007, a decrease of 38 percent from FY 2006. Chart 1 shows the number of new infected and source flocks by year. The total infected and source flock statuses that were released in FY 2007 was 83. Three hundred, thirty-one positive scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) for FY 2007. Of these, 59 were RSSS cases, collected in FY 2007, 253 positive field cases, six test validation necropsies, and 13 third eyelids tests. One of the field cases was a goat. Five cases were consistent with Nor98 scrapie (Figure 1).
Approximately 3,622 animals were indemnified comprised of 61 percent non-registered sheep, 35 percent registered sheep, 2.3 percent non-registered goats and 1.7 percent registered goats. Regulatory Scrapie Slaughter Surveillance (RSSS) RSSS was designed based on the findings of the Center for Epidemiology and Animal Health (CEAH) Scrapie: Ovine Slaughter Surveillance (SOSS) study. The results of SOSS can be found at www.aphis.usda.gov/vs/ceah/cahm/sheep/sheep.htm. RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks for cleanup. During FY 2007, collections increased by 11 percent overall and by 16 percent for black and mottled faced sheep compared to FY2006. Improvement in the overall program effectiveness and efficiency is demonstrated by the 34 percent decrease in percent positive black faced sheep compared to FY 2006 (.44 to .29 percent, based on test results posted before October 12, 2007). During FY 2007, 41,244 samples were collected (Figure 2). There have been 59 NVSL confirmed positive cases collected in FY2007. Face colors of these positives were 46 black, 11 mottled, one white and one unknown. The percent positive by face color is shown in Figure 3 below.
Caprine Scrapie Prevalence Study (CSPS)
CSPS was initiated in May 2007, to estimate the national prevalence of scrapie in adult goats at slaughter. If no scrapie is found we will be able to conclude that the prevalence is less than 0.1 percent. As of September 30, 2007, 1,515 goats were sampled for scrapie testing. None had tested positive for scrapie.
Scrapie Testing
As of September 30, 2007, 47,697 animals have been sampled for scrapie testing: 41,244 RSSS, 1,515 goats for the CSPS, 3,557 regulatory field cases, 139 necropsy validations, and 1,242 regulatory third eyelid biopsies.
Scrapie USA 2008
Infected and Source Flocks As of September 30, 2008, there were 31 scrapie infected and source flocks, a decrease of 16 percent from September 30, 2007. There were a total of 61 new infected and source flocks reported for FY 2008, a decrease of 15 percent from FY 2008. Chart 1 shows the number of new infected and source flocks by year. The total infected and source flock statuses that were released in FY 2008 was 64. 174 positive scrapie cases were confirmed and reported by the National Veterinary Services Laboratories (NVSL) for FY 2008. Of these, 40 were RSSS cases, (collected in FY 2008), 128 positive field necropsy cases, 4 rectal biopsy and 2 third eyelid tests. Five of the field cases were goats that originated from the same herd. One RSSS case was consistent with Nor98 scrapie. NOTE: Ante-mortem scrapie testing in sheep and goats using rectal biopsy was approved for program use by USDA for in January 2008. Approximately 2,438 animals were indemnified comprised of 51.4 percent non-registered sheep, 30.5 percent registered sheep, 9.6 percent non-registered goats and 8.5 percent registered goats.
Scrapie USA 2009
PROCEEDINGS ONE HUNDRED AND THIRTEENTH ANNUAL MEETING of the United States Animal Health Association
2009
National Scrapie Surveillance Plan Implementation: The National Scrapie Surveillance Plan is posted at http://www.aphis.usda.gov/vs/nahss/sheep/national_scrapie_surveillance_plan_08192008.pdf.
The plan provides a comprehensive review of scrapie surveillance in the U.S., explains the basis for implementing state-of-origin sampling targets and ultimately flock level surveillance, and establishes minimum targets for FY 2009 and 2010. In FY 2009, Area Action Plans were developed to help meet state-of-origin sampling and ID compliance targets identified by the National Scrapie Surveillance Plan. This activity resulted in increased sampling in states not meeting plan targets.
Infected and Source Flocks: Thirty-three percent fewer newly infected and source flocks were identified in FY 2009 through July compared to the same month in FY 2008 (Figure 1). As of July 31, 2009, there were 21 scrapie infected and source flocks with open statuses. In FY 2009, 21 new source flocks and 8 new infected flocks had been reported; 26 flocks had completed a clean-up plan and been released. The ratio of infected and source flocks released to newly identified infected and source flocks for FY 2009 = 0.9 : 1.
Positive Scrapie Cases: As of July 31, 2009, 65 positive cases in sheep or goats were reported by the National Veterinary Services Laboratories (NVSL); 34 were field cases and 31 were RSSS cases collected between October 1, 2008 and July 31, 2009 and confirmed by August 20, 2009. Field cases are positive animals tested as part of a disease investigation including potentially exposed, exposed and suspect animals. Twenty cases of scrapie in goats have been confirmed by NVSL since implementation of the regulatory changes in FY 2002. The most recent positive goat case was confirmed in July 2009 and is epidemiologically linked to the same herd in Michigan as the positive goat cases that were found in FY 2008. The positive goat was a pet animal quarantined as part of the FY 2008 investigation. No additional animals were exposed.
Regulatory Scrapie Slaughter Surveillance (RSSS): RSSS started April 1, 2003. It is a targeted slaughter surveillance program which is designed to identify infected flocks. Samples have been collected from 223,452 animals since April 1, 2003: this total includes 695 rectal biopsies collected in Texas as part of a surveillance pilot project. There have been 415 NVSL confirmed positive animals since the beginning of RSSS. As of July 31, 2009, 34,193 samples, including 513 rectal biopsies, have been collected in FY 2009. Thirty one samples collected in FY 2009 have tested positive for scrapie; 28 of these were from black-faced sheep and 3 from mottle-faced sheep. Two of these RSSS cases originated from a source flock identified at the end of FY 2008. Four other animals originated from flocks containing other RSSS positive sheep. There was an 11% decrease in percent positive black face sheep sampled at slaughter (.18 to .16%) between FY 2008 and FY 2009 as of July 31, 2009 if multiple positives from the same flock are excluded (Figure 2). RSSS was designed based on the findings of the Center for Epidemiology and Animal Health (CEAH), Scrapie: Ovine Slaughter Surveillance (SOSS) study. The results of SOSS can be found at http://www.aphis.usda.gov/vs/ceah/cahm/Sheep/sheep.htm.
Scrapie Testing: As of July 31, 2009, 36,524 animals have been sampled for scrapie testing: 34,193 RSSS samples (number includes 513 rectal biopsies from Texas), 1,663 regulatory field cases, and 668 liveanimal biopsies.
Scrapie USA 2010
Positive Scrapie Cases:
• As of September 30, 2010, 72 cases of classical scrapie and 5 cases of Nor98-like scrapie were confirmed by the National Veterinary Services Laboratories (NVSL); 53 were field cases and 24 were RSSS cases collected between October 1, 2009 and September 30, 2010 and confirmed by November 8, 2010. Of the five Nor98-like scrapie cases, four were RSSS cases that originated from flocks in Ohio, Pennsylvania, Oregon, and Idaho and one was a field case form Maine. This brings the total number of Nor98-like cases detected in the United States to 11. Field cases are positive animals tested as part of a disease investigation including potentially exposed, exposed, and suspect animals or tested as part of on farm surveillance.
Scrapie USA 2011
Positive Scrapie Cases: ???
PROCEEDINGS ONE HUNDRED AND FIFTEENTH ANNUAL MEETING of the UNITED STATES ANIMAL HEALTH ASSOCIATION
2011
National Scrapie Eradication Program
Diane Sutton, United States Department of Agriculture, Animal and Plant Health Inspection Service, Veterinary Services (USDA-APHIS-VS) gave the following update of the scrapie eradication program:
Scrapie Eradication Program Results
• There has been a 96% decrease in the percent positive sheep sampled at slaughter adjusted for face color, from 0.16 to 0.0067%, since the start of Regulatory Scrapie Slaughter Surveillance (RSSS) in FY 2003 thru Aug. 31, 2011.
• A decrease of 40% newly infected and source flocks was reported in FY 2011 through August compared to the same date in FY 2010. • At the current rate of progress, we expect the prevalence to be at or near zero for FY 2017.
Slaughter Surveillance
• The number of animals sampled through slaughter surveillance in FY 2011, through Aug. 31, 2011, was 34,146 a decrease from 42,104 in FY 2010 — a decrease of 19%. The decline was primarily due to strict adherence to targeting criteria to reduce testing costs.
2011
*** After a natural route of exposure, 100% of white-tailed deer were susceptible to scrapie.
Scrapie USA 2012
Positive Scrapie Cases ???
Scrapie Eradication Program Results
• There has been a 96 percent decrease in the percent positive sheep sampled at slaughter adjusted for face color, from 0.15 to 0.0057 percent, since the start of Regulatory Scrapie Slaughter Surveillance (RSSS) in FY2003 thru September 30, 2012.
• There were eight new infected or source flocks reported in FY2012 as of September 30, 2012. A decrease of 47 percent compared to the same date in FY 2011.
Slaughter Surveillance
• The number of animals sampled through slaughter surveillance in FY 2012 through September 30, 2012 was 40,776 compared to 37,192 in FY2011; this represents an increase of 10 percent. The increase was due in part to increased sampling of goats.
Scrapie 2013
Positive Scrapie Cases: ???
Scrapie Surveillance Projects:
• Since the start of slaughter surveillance in 2003 the prevalence of scrapie in sheep has declined 85 percent from 0.2 percent to less than 0.03 percent. The prevalence in goats is estimated to be less than 0.02 percent.
• APHIS continues to find new approaches to increase flock level surveillance.
• In FY 2013 APHIS initiated an effort to provide information on sample collection and to encourage producer and accredited veterinarian submission of samples.
• Instructions for producers and veterinarians to submit samples are now available on the APHIS Scrapie Web Page.
• In FY 2014 APHIS will conduct pilot projects in New Jersey and Arkansas to evaluate the efficiency of working with accredited veterinarians to collect samples for scrapie testing.
Update from Agriculture Research Service
David Schneider
USDA, Agriculture Research Service (ARS), Animal Disease Research Unit
(ADRU)
The USDA-ARS unit in Pullman, Washington, conducts an integrated research program involving studies on scrapie transmission, diagnosis and susceptibility genetics in domestic sheep and goats. Accumulation of diseaseassociated prion protein (PrPSc) in the placenta of sheep is a recognized source for natural transmission of classical scrapie disease and environmental contamination. Much less is known about prion accumulation in the placenta of goats but our recent study demonstrated much less PrPSc accumulates in the placenta in goats, which calls into question its role in natural transmission. In a recent follow-up study, we now demonstrate that the placenta of goats does harbor prions infectious to other goats and sheep when exposed by the oral route. A study on Nor98-like scrapie in breeding ewes is now in its 6th year.
REPORT OF THE COMMITTEE
344
Ewes were experimentally inoculated with brain homogenate obtained from a U.S. sheep with clinical Nor98-like scrapie. Recipient ewes are bred annually to examine the placenta for evidence of a transmissible agent. Placentas shed 2009-2013 were negative. In 2013, one recipient ewe developed an unrelated disease. At postmortem examination, abundant accumulation of PrPSc was observed only in the cerebellum of this ewe with much less accumulation in the hindbrain obex. This confirms that initial inoculation of these ewes has been successful. Monitoring continues in the remaining ewes of this study. Improvements in tissue-based (rectal biopsy) live animal testing for scrapie with focus on application to goats continue. In addition, efforts toward developing a live-animal blood test have demonstrated the presence of prions (infectivity) in the blood of sheep and goats, even those with preclinical disease and within blood sample volumes routinely used in veterinary diagnostic work. A recent study also demonstrates PrPSc accumulation in lymphoid tissues of hemal nodes, small lymphoid organs that filter blood but not lymph.
Collectively, these findings confirm that blood is a relevant target for continued assay development. We continue to develop methods for enriching the relevant blood fractions for assay and are now making efforts to adapt novel in vitro assays for detecting infectivity and prion-associated misfolding activity. A long term study examining the effect of prion genotype on susceptibility to goat scrapie and the effect of genetic changes on accuracy of live animal testing continue. Following oral infection at birth with placenta and brain-derived scrapie, goats with the highly susceptible genotype all developed clinical disease around 24 months. Goats with the less susceptible or long incubation genetics today remain clinically normal. Monitoring continues.
Prion Transmission Through Milk
Christina Sigurdson
University of California, San Diego School of Medicine, Department of Pathology
Prion disorders are caused by misfolded proteins that are naturally transmitted, causing a fatal neurological disease in animals. In sheep with classical scrapie, prions accumulate in the follicles of lymphoid tissues in addition to the brain and spinal cord. Follicular dendritic cells (FDCs) form a network within the follicles and accumulate high levels of prions during disease. Previous work in mice has revealed that follicular inflammation in nonlymphoid organs, such as kidney, results in prion accumulation and can lead to prion shedding, such as into the urine. We have found sheep with follicular mastitis and scrapie that have accumulated prions within the follicles of the mammary gland.
In follow-up studies, we found that sheep with scrapie and lentiviral mastitis secrete prions into the milk and infect nearly 90% of naïve suckling lambs. Taken together, lentiviruses may enhance prion transmission and conceivably sustain prion infections in flocks for generations. Work by other groups has also shown prion infectivity in all three milk fractions, cells, casein whey, and
SCRAPIE 345
cream. Prion infectivity has also been detected in milk from sheep having the VRQ/VRQ genotype with no evidence of mastitis.
References
1. Konold, T., Moore, S.J., Bellworthy, S.J. & Simmons, H.A. Evidence of scrapie transmission via milk. BMC Vet Res 4, 14 (2008). 2. Konold, T., et al. Evidence of effective scrapie transmission via colostrum and milk in sheep. BMC Vet Res 9, 99 (2013). 3. Ligios, C., et al. Sheep with Scrapie and Mastitis Transmit Infectious Prions through the Milk. J Virol 85, 1136-1139 (2011). 4. Ligios, C., et al. PrPSc in mammary glands of sheep affected by scrapie and mastitis. Nat Med 11, 1137-1138 (2005). 5. Lacroux, C., et al. Prions in milk from ewes incubating natural scrapie. PLoS Pathog 4, e1000238 (2008).
Committee Business:
The final response from the Committee’s 2012 Resolution (26, 9 and 30 Combined) relating to the export of sheep and goats was reviewed. In this response the USDA-APHIS-VS agreed to ask the World Organization for Animal Health (OIE) to modify the Scrapie Chapter to consider options such as genotyping to qualify animals for export. USDA-APHIS-VS agreed to make this request by Spring 2014, and would expect to see the Scrapie Chapter amended in Spring 2015 or 2016 if their revisions were to be accepted by OIE. One of the Committee members updated the group on progress related to a 2010 Resolution #48. This resolution requested USDA, Food Safety Inspection Service (FSIS) to work with USDA-APHIS-VS and industry to identify and approve appropriate sites for radio frequency identification implants for goats and sheep. As a result, both the underside of the tail and the base of the ear are now approved sites for these implants. No new resolutions or recommendations were introduced. The Committee briefly discussed the challenges of obtaining scrapie surveillance samples from certain flocks and herds. Several members mentioned that one barrier to sample collection is the problem that the producers have with carcass disposal after the head has been removed. Members agreed that offering options to producers to help them properly dispose of these carcasses could significantly increase voluntary participation in surveillance. Options include to transporting carcasses to diagnostic laboratories or providing payment to the producers to offset the cost of carcass disposal.
Scrapie 2015
Positive Scrapie Cases ???
Scrapie Eradication Program Results
• The National Scrapie Eradication Program continued to make progress in FY 2015.
• At the end of FY 2014, the percent of cull sheep found positive at slaughter and adjusted for face color was 0.018 percent and is currently at 0.004 percent for FY 2015. This measure has decreased by 80 percent compared to FY 2014 and by 98 percent compared to FY 2003.
• Three source flocks and 3 infected flocks were designated in FY 2014. One infected and three source flocks have been designated in FY 2015, a decrease of 30 percent.
• In November 2014, the first positive goat found through RSSS was identified. Based on the goats sampled at slaughter to date, the prevalence of scrapie in U.S. cull goats (2003 – 2015) was 0.0037 percent with an upper 95 percent confidence limit of 0.0097 percent.
• In FY 2015 there was a decrease in the number of States meeting their sampling minimums for sheep and goats. This was likely due in part to the impact of Highly Pathogenic Avian Influenza response on resources.
Slaughter Surveillance
As of September 30, 2015, 40,862 animals were sampled for scrapie testing in FY 2015:
• 38,671 RSSS samples and 2,191 on-farm samples;
• Of which 33,698 were sheep and 7,164 were goats.
Sunday, October 25, 2015
USAHA Detailed Events Schedule – 119th USAHA Annual Meeting CAPTIVE LIVESTOCK CWD SCRAPIE TSE PRION
Scrapie USA 2016
Scrapie Eradication Program Results*
The National Scrapie Eradication Program continued to make progress in FY 2016.
As a result of the hard work of industry, the states and APHIS, we have decreased scrapie prevalence in cull sheep from 1 in 500 to less than 1 in 20,000 (based on upper confidence level). At the end of FY 2015, the percent of cull sheep found positive at slaughter and adjusted for face color was 0.0036 percent. As of September 30, 2016, this measure was 0.0014 percent (upper confidence limit 0.005%) a 61 percent decrease; however, due to sample size this is not significantly different from FY 2015.
At the end of FY 2015, the percent of cull black face sheep found positive at slaughter was 0.025 percent. The current value of this measure is 0.009 percent, a 99 percent decrease compared to FY 2003 and a 62 percent decrease from FY 2015. The upper confidence limit of the measure is 0.025 percent so the change from FY 2015 is not statistically significant.
One infected and three source flocks were designated in FY 2015. Two infected and three source flocks have been designated in FY 2016.
In November 2014, the first positive goat found through Regulatory Scrapie Slaughter Surveillance (RSSS) was identified. Based on all goats sampled at slaughter, the prevalence of scrapie in U.S. cull goats is 0.003 percent with an upper 95 percent confidence limit of 0.011 percent. To date, no other goats have tested positive at slaughter.
Slaughter Surveillance*
As of September 30, 2016, 39,978 animals have been sampled for scrapie testing in FY 2016:
• 37,878 RSSS samples and 2,100 on-farm samples;
• Of which 32,356 were sheep and 7,622 were goats.
Texas Scrapie Confirmed in a Hartley County Sheep where CWD was detected in a Mule Deer
April 22, 2016
Scrapie Confirmed in a Hartley County Sheep
AUSTIN - Texas Animal Health Commission (TAHC) officials have confirmed scrapie in a Hartley County ewe. The ewe was tested by TAHC after the owner reported signs of weight loss and lack of coordination to their local veterinarian. The premises was quarantined and a flock plan for monitoring is being developed by the TAHC and USDA.
"The TAHC is working closely with the flock owner, sharing all of the options for disease eradication," said Dr. David Finch, TAHC Region 1 Director. "We are thankful the producer was proactive in identifying a problem and seeking veterinary help immediately."
Texas leads the nation in sheep and goat production. Since 2008, there have been no confirmed cases of scrapie in Texas. The last big spike in Texas scrapie cases was in 2006 when nine infected herds were identified and the last herd was released from restrictions in 2013.
According to USDA regulations, Texas must conduct adequate scrapie surveillance by collecting a minimum of 598 sheep samples annually. Since USDA slaughter surveillance started in FY 2003, the percent of cull sheep found positive for scrapieat slaughter (once adjusted for face color) has decreased 90 percent.
Scrapie is the oldest known transmissible spongiform encephalopathies, and under natural conditions only sheep and goats are known to be affected by scrapie. It is a fatal disease that affects the central nervous system of sheep and goats. It is not completely understood how scrapie is passed from one animal to the next and apparently healthy sheep infected with scrapie can spread the disease. Sheep and goats are typically infected as young lambs or kids, though adult sheep and goats can become infected.
The most effective method of scrapie prevention is to maintain a closed flock. Raising replacement ewes, purchasing genetically resistant rams and ewes,or buying from a certified-free scrapie flock are other options to reduce the risk of scrapie. At this time the resistant genetic markers in goats have not been identified, therefore it is important to maintain your sheep and goat herds separately.
The incubation period for Scrapie is typically two to five years. Producers should record individual identification numbers and the seller's premise identification number on purchase and sales records. These records must be maintained for a minimum of five years.
Producers should notify the Texas Animal Health Commission (800-550-8242) or the USDA-Austin Office (512-383-2400) if they have an adult sheep or goat with neurologic signs such as incoordination, behavioral changes, or intense itching with wool loss. Producers may order scrapie identification tags by calling 866-873-2824. For more information, please visit our website at:
TEXAS Sheep and Goats
• Most recent scrapie positive animal in Texas was found in April, 2008.
• USDA-APHIS-VS set the national goal for surveillance at 46,000 traceable, mature sheep or goats. Target for Texas is 1,472.
• The Scrapie Program Review is being scheduled for this summer. No problems expected.
Scrapie USA 2017
REPORT OF THE SUBCOMMITTEE ON SCRAPIE
Chair: Cheryl Miller, IN
Vice Chair: Larry Forgey, MO
The Subcommittee met on October 18, 2017 at the Town and Country Hotel in San Diego, California from 9:00 a.m. to 12:35 p.m. There were 21 members and 14 guests present. Meeting was called to order by the chairman, Dr. Cheryl Miller. All attendees were asked to sign in.
Presentations and Reports
Scrapie Program Updates
Diane Sutton, USDA-APHIS-VS
Scrapie Eradication Program Results*
• The National Scrapie Eradication Program made tremendous progress in FY2017.
• Other than a goat that resided in a herd that was under quarantine since 2005 there have been no classical scrapie positive animals in the United States since April 2016. This goat herd was depopulated in July and the remaining goats moved to the Agricultural Research Service (ARS).
• There were two Nor98-like cases confirmed by the National Veterinary Services Laboratory (NVSL) one from Colorado and one with a Montana tag pending trace back.
• The last two known scrapie infected/source flocks have been depopulated and the premises are pending disinfection. No high-risk animals exist in the United States outside of research facilities. Surveillance*
• As of September 30, 2017, 42,030 animals had been sampled for scrapie testing in FY2017:
• 6 percent were collected on-farm and 94 percent through Regulatory Scrapie Slaughter Surveillance (RSSS)
• 19 percent of the samples collected were from goats and the 81 percent from sheep
• Implementation FY2018
• States with RSSS collection sites will continue to sample targeted sheep and goats.
• The State sampling minimums for FY2018 have been provided to the States and will be made public in the October monthly report. Note: These are minimums. The plan is to continue to collect samples from the maximum number of targeted animals given the available budget.
Scrapie USA 2018
Scrapie Program Updates
Diane Sutton, USDA-APHIS, Veterinary Services (VS)
Scrapie Eradication Program Results*
• The National Scrapie Eradication Program made progress in FY2018.
• The last confirmed classical scrapie positive sheep was in April 2016.
• In April 2018, APHIS identified scrapie in a 171 RR sheep from a flock in North Carolina. There was insufficient positive tissue available to rule out non-classical scrapie; the flock has been depopulated and no other sheep in the flock have tested positive for scrapie. USDA continues to conduct additional testing, before determining whether to classify the case as classical or non-classical scrapie.
• In August 2018, a Pennsylvania goat sampled at slaughter in July was confirmed positive for classical scrapie. The flock is scheduled for high-risk animal depopulation in October 2018. The only other positive goat found through slaughter surveillance was in November 2014.
• One Nor98-like case sampled in October 2017 was confirmed positive. Unlike classical scrapie, non-classical scrapie (Nor98-like) is either not laterally transmissible or is transmissible at a very low rate. The World Animal Health Organisation (OIE) and APHIS have determined that it is not a disease of trade concern Surveillance*
• Since the scrapie slaughter surveillance program began in FY2003, over 600,000 samples have been collected.
• As of September 30, 2018, 43,625 animals had been sampled for scrapie testing in FY2018:
o 5% were collected on-farm and 95 percent through RSSS
o 21% of the samples collected were from goats and the 79% from sheep
• When first measured in FY2002-2003, the percentage of cull sheep sampled at slaughter that tested positive for classical scrapie was 1 in 500. Since the last case in April 2016, APHIS has tested 82,199 sheep and no cases of classical scrapie have been confirmed.
• Since the slaughter surveillance program began, only two goats sampled at slaughter have been confirmed positive for classical scrapie, one sampled in FY2015 and one in FY2018. Since the detection in FY2015, 25,618 goats have been tested through slaughter surveillance.
USDA-APHIS FY 2018 Cervid Health Program Update
Tracy Nichols, USDA-APHIS, Veterinary Services (VS)
The USDA Chronic Wasting Disease (CWD) Herd Certification Program (HCP) is a voluntary program in which herd certification is required for interstate movement of farmed cervids. Certification requires five years of 100 percent CWD post mortem testing of all herd mortalities over 12 months of age and zero CWD detection. This program was implemented in 2014 after the approval of the final CWD rule.
Management of this program is a collaborative effort between USDAAPHIS and States, with State participation being voluntary. Currently 28 states participate in the program encompassing 2,393 enrolled herds, and 1,875 certified herds. Of the certified herds, 1,434 are deer, 344 elk, and 97 mixed (containing both deer and elk). In fiscal year 2018 there were 15 newly identified farmed cervid herds (11 deer, 1 elk, 1 reindeer, and 2 mixed). Six of the 15 herds were HCP-certified, and two were enrolled. The remaining seven were not part of the program. Ten of the newly identified herds were located in areas endemic with CWD.
snip...
Interspecies Transmission of the Scrapie Agent
Justin Greenlee, National Animal Disease Center (NADC), Agricultural Research Service (ARS), USDA
The Virus and Prion Research Unit at the National Animal Disease Center has ongoing research projects with the agents of scrapie, bovine spongiform encephalopathy (BSE), and chronic wasting disease (CWD). Numerous studies have been done to better understand scrapie strains and their potential to transmit to other species. We acknowledge at least two scrapie strains present in the U.S. In previous studies we used two scrapie isolates: No. 13-7 that was isolated from ARQ/ARQ black-faced sheep and x124 that has a rapid incubation time in sheep with the V136 allele. Studies that have been conducted in cats, cattle, pigs, and raccoons suggest a substantial barrier to transmission based upon incomplete attack rates, prolonged incubation, or limited distribution of abnormal prion protein in the body. However, the No. 13-7 scrapie agent transmits to white-tailed deer after intracranial of oronasal challenge with a 100% attack rate. We conducted a study to determine if deer infected with the scrapie agent could serve as a reservoir of scrapie infectivity to sheep. The scrapie agent from deer did transmit to sheep by the oronasal route, but with more rapid incubation periods in sheep with the V136 genotype and with lesions consistent with x124 scrapie rather than the original No. 13-7 inoculum. Very low incidence of scrapie in the U.S. suggests that exposure of deer to the scrapie agent is unlikely. If sheep were exposed to the scrapie agent from deer, current genotype-based methods for scrapie eradication would remain effective.
Update on Scrapie Research at the Animal Disease Research Unit David Schneider, USDA, Agricultural Research Service (ARS)
The USDA-ARS Animal Disease Research Unit in Pullman, Washington, conducts an integrated research program involving studies on scrapie diagnostics, the role of Prion Protein (PRNP) genetics, and modes of transmission in domestic sheep and goats. In this update, we report on the role of goat milk and concurrent SRLV-infection on transmissibility of scrapie to goat kids and lambs; an update of ongoing research to determine the role of PRNP genetics on susceptibility and disease on diagnostics in goats and sheep; and initiation of an attempt to isolate a prion (infectious particle) from of a young resistant-genotype sheep with peripheral accumulation of PrP-Sc.
Classical scrapie was transmitted to goat kids and lambs after lowvolume, short-duration bottle feeding of mid-lactation milk from goat does with naturally acquired scrapie and small ruminant lentivirus (SRLV) infections. The potential role of concurrent SRLV infection was explored and results were consistent with a virus-associated increase in PrP-Sc accumulation in the mammary glands of the milk donor goats and the likelihood of scrapie transmission. SRLV was also transmitted to some of the goat kids but not lamb milk recipients, however, SRLV transmission did not appear to be necessary for scrapie transmission.
Goats bearing the PRNP codons NS146 or QK222 and orally inoculated at birth with goat-derived scrapie continued to be monitored for signs of scrapie transmission. At more than eight years post-inoculation, four of eight NS146 goats still survive and are in good health. However, the last two of eight QK222 goats were euthanized because of ageing dentition. No evidence of PrP-Sc accumulation has been observed. Monitoring of the surviving NS146 goats continues.
A survey study on archived tissue of classical scrapie in U.S. sheep covering the years 2000-2007 was completed. The PRNP genotype of these sheep was expanded to include the amino acid at codon 112 (M or T). Diagnosis of scrapie was significantly less likely in heterozygous MT112 sheep (7% prevalence) than in homozygous MM112 (wild type) sheep (37% prevalence) and no cases of scrapie were detected in 27 sheep genotyped to be homozygous TT112. While uniformity of exposure cannot be known, the data suggest the T112 allele confers some resistance to scrapie infection, but not strong enough to fully protect the heterozygous animal. Other data suggest that the T112 allele may reduce the peripheral accumulation of PrPSc, perhaps making these animals more difficult to detect early in disease progression.
Subcommittee Business:
snip...
Ohio Scrapie Cases in Goats FY 2002 – FY 2021
Ohio atypical scrapie Nor-98 TSE Prion detected 2010 1 case documented
THURSDAY, JANUARY 7, 2021
Atypical Nor-98 Scrapie TSE Prion USA State by State Update January 2021
Second passage of chronic wasting disease of mule deer in sheep compared to classical scrapie after intracranial inoculation
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Second passage of chronic wasting disease of mule deer in sheep compared to classical scrapie after intracranial inoculation
Author item Cassmann, Eric item FRESE, RYLIE - Orise Fellow item Greenlee, Justin Submitted to: Journal of Veterinary Diagnostic Investigation Publication Type: Peer Reviewed Journal Publication Acceptance Date: 11/25/2020 Publication Date: N/A Citation: N/A
Interpretive Summary: Chronic wasting disease (CWD) is a fatal and uncurable brain disease of deer and elk that is related to a similar disease in sheep called scrapie. Both diseases are cause by a misfolded protein called a prion. The exact origin of CWD is unknown, but a possible origin could have been spread of sheep scrapie to deer. Previous research found indistinguishable traits in common between CWD in deer and scrapie in sheep. Additionally, it is unknown if deer CWD can naturally transmit to sheep. In this research, we show that abnormal prions spread throughout the body of sheep intracranially infected with CWD similar to how scrapie spreads in sheep. We compared two US classical scrapie strains to CWD in sheep and found that one of these strains is indistinguishable from sheep CWD. These results demonstrate that current diagnostic techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred in a natural setting. This research reinforces the need to continue ongoing cross-species transmission studies focusing on oral susceptibility of sheep to CWD and develop techniques to discriminate sheep CWD from sheep scrapie.
Technical Abstract: The origin of chronic wasting disease (CWD) in cervids is unclear. One hypothesis suggests that CWD originated from scrapie in sheep. In this experiment, we had two main objectives. The first objective was to determine if CWD adaptation in sheep alters the disease phenotype. The second objective was to determine if the disease phenotype of sheep adapted CWD is distinct from classical scrapie. We intracranially inoculated sheep with brain homogenate from first passage mule deer CWD in sheep (sCWDmd). The attack rate in second passage sheep was 100% (12/12). Sheep had prominent lymphoid accumulations of PrPSc reminiscent of classical scrapie. The pattern and distribution of PrPSc in the brains of sheep with CWDmd was similar to scrapie strain 13-7 but different from scrapie strain x124. The western blot glycoprofiles of sCWDmd were indistinguishable from scrapie strain 13-7; however, independent of sheep genotype, glycoprofiles of sCWDmd were different than x124. When sheep genotypes were evaluated individually, there was considerable overlap in the glycoprofiles that precluded significant discrimination between sheep CWD and scrapie strains. Taken together, these data suggest that the phenotype of CWD in sheep is indistinguishable from some strains of scrapie in sheep. Given the results of this study, current diagnostic techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally. It is unknown if sheep are naturally vulnerable to CWD; however, the susceptibility of sheep after intracranial inoculation and lymphoid accumulation indicates that the species barrier is not absolute.
''We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n=5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation.'' Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease Authors
item Greenlee, Justin item Moore, S – item Smith, Jodi – item Kunkle, Robert item West Greenlee, M –
Submitted to: American College of Veterinary Pathologists Meeting Publication Type: Abstract Only Publication Acceptance Date: August 12, 2015 Publication Date: N/A
Technical Abstract: The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n=5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral cortex had a profile similar to the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph nodes revealed PrPSc with a higher profile resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical scrapie were further passaged to mice expressing cervid prion protein and intranasally to sheep and WTD. In cervidized mice, the two inocula have distinct incubation times. Sheep inoculated intranasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum that had a scrapie-like profile. The WTD study is ongoing, but deer in both inoculation groups are positive for PrPSc by rectal mucosal biopsy.
In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, two distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile readily passes to deer.
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies
Location: Virus and Prion Research
Title: Passage of scrapie to deer results in a new phenotype upon return passage to sheep) Author
item Greenlee, Justin item Kokemuller, Robyn item Moore, Sarah item West Greenlee, N
Submitted to: Prion
Publication Type: Abstract Only
Publication Acceptance Date: 3/15/2017
Publication Date: N/A
Citation: N/A
Interpretive Summary:
Technical Abstract: Aims: We previously demonstrated that scrapie has a 100% attack rate in white-tailed deer after either intracranial or oral inoculation. Samples from deer that developed scrapie had two different western blot patterns: samples derived from cerebrum had a banding pattern similar to the scrapie inoculum, but samples from brainstem had a banding pattern similar to CWD. In contrast, transmission of CWD from white-tailed deer to sheep by the intracranial route has a low attack rate and to-date oronasal exposure has been unsuccessful. The purpose of this study was to determine if sheep are susceptible to oronasal exposure of the scrapie agent derived from white-tailed deer.
Methods: At approximately 5 months of age, Suffolk sheep of various PRNP genotypes were challenged by the oronasal route with 10% brain homogenate derived from either the cerebrum or the brainstem of scrapie-affected deer. Genotypes represented in each inoculation group were VV136RR154QQ171 (n=2), AA136RR154QQ171 (n=2), and AV136RR154QR171 (n=1). After inoculation, sheep were observed daily for clinical signs. Upon development of clinical signs, sheep were killed with an overdose of pentobarbital sodium and necropsied. Tissue samples were tested for the presence of PrPSc by EIA, western blot, and immunohistochemistry (IHC). The No. 13-7 scrapie inoculum used for the deer has a mean incubation period of 20.1 months in sheep with the AA136RR154QQ171 genotype and 26.7 months in sheep with the VV136RR154QQ171 genotype.
Results: Sheep inoculated oronasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum from the cerebrum that had a scrapie-like profile. The first sheep to develop clinical signs at approximately 29 months post inoculation had the VV136RR154QQ171 genotype. Eventually sheep of the AA136RR154QQ171 genotype developed clinical signs, but at a mean incubation of 52 months. At 62 months post-inoculation, none of the sheep inoculated with material from the deer brainstem have developed clinical disease.
Conclusions: The No. 13-7 inoculum used in the original deer experiment readily infects white-tailed deer and sheep of various genotypes by the oronasal route. When inoculum is made from different brain regions of No 13-7 scrapie-infected deer from either cerebrum with a scrapie-like western blot pattern or brainstem with a CWD-like western blot pattern, sheep with the VV136RR154QQ171 genotype are the first to develop clinical signs. This is in contrast to the original No. 13-7 inoculum that has a faster incubation period in sheep with the AA136RR154QQ171 genotype. Similar to experiments conducted with CWD, sheep oronasally inoculated with brainstem material from deer with a CWD-like molecular profile have no evidence of disease after 62 months of incubation. While scrapie is not known to occur in free-ranging populations of white-tailed deer, experimental cases are difficult to differentiate from CWD. This work raises the potential concern that scrapie infected deer could serve as a confounding factor to scrapie eradication programs as scrapie from deer seems to be transmissible to sheep by the oronasal route.
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Title: Transmission of the agent of sheep scrapie to deer results in PrPSc with two distinct molecular profiles
Authors item Greenlee, Justin item Moore, Sarah - item Smith, Jodi item West Greenlee, Mary - item Kunkle, Robert Submitted to: Prion Publication Type: Abstract Only Publication Acceptance Date: March 31, 2015 Publication Date: May 25, 2015 Citation: Greenlee, J., Moore, S.J., Smith, J.., West Greenlee, M.H., Kunkle, R. 2015.
Scrapie transmits to white-tailed deer by the oral route and has a molecular profile similar to chronic wasting disease and distinct from the scrapie inoculum.
Prion 2015. p. S62.
Technical Abstract: The purpose of this work was to determine susceptibility of white-tailed deer (WTD) to the agent of sheep scrapie and to compare the resultant PrPSc to that of the original inoculum and chronic wasting disease (CWD). We inoculated WTD by a natural route of exposure (concurrent oral and intranasal (IN); n=5) with a US scrapie isolate. All scrapie-inoculated deer had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues at preclinical time points, and deer necropsied after 28 months post-inoculation had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues. Western blotting (WB) revealed PrPSc with 2 distinct molecular profiles. WB on cerebral cortex had a profile similar to the original scrapie inoculum, whereas WB of brainstem, cerebellum, or lymph nodes reveal PrPSc with a higher profile resembling CWD. Homogenates with the 2 distinct profiles from WTD with clinical scrapie were further passaged to mice expressing cervid prion protein and intranasally to sheep and WTD. In cervidized mice, the two inocula have distinct incubation times. Sheep inoculated intranasally with WTD derived scrapie developed disease, but only after inoculation with the inoculum that had a scrapie-like profile. The WTD study is ongoing, but deer in both inoculation groups are positive for PrPSc by rectal mucosal biopsy.
In summary, this work demonstrates that WTD are susceptible to the agent of scrapie, two distinct molecular profiles of PrPSc are present in the tissues of affected deer, and inoculum of either profile type readily passes to deer.
White-tailed Deer are Susceptible to Scrapie by Natural Route of Infection
Jodi D. Smith, Justin J. Greenlee, and Robert A. Kunkle; Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS
Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. Previous experiments demonstrated that white-tailed deer are susceptible to sheep-derived scrapie by intracranial inoculation. The purpose of this study was to determine susceptibility of white-tailed deer to scrapie after a natural route of exposure. Deer (n=5) were inoculated by concurrent oral (30 ml) and intranasal (1 ml) instillation of a 10% (wt/vol) brain homogenate derived from a sheep clinically affected with scrapie. Non-inoculated deer were maintained as negative controls. All deer were observed daily for clinical signs. Deer were euthanized and necropsied when neurologic disease was evident, and tissues were examined for abnormal prion protein (PrPSc) by immunohistochemistry (IHC) and western blot (WB). One animal was euthanized 15 months post-inoculation (MPI) due to an injury. At that time, examination of obex and lymphoid tissues by IHC was positive, but WB of obex and colliculus were negative. Remaining deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 MPI. Tissues from these deer were positive for scrapie by IHC and WB. Tissues with PrPSc immunoreactivity included brain, tonsil, retropharyngeal and mesenteric lymph nodes, hemal node, Peyer’s patches, and spleen. This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by potential natural routes of inoculation. In-depth analysis of tissues will be done to determine similarities between scrapie in deer after intracranial and oral/intranasal inoculation and chronic wasting disease resulting from similar routes of inoculation.
see full text ;
PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
White-tailed deer are susceptible to the agent of sheep scrapie by intracerebral inoculation
snip...
It is unlikely that CWD will be eradicated from free-ranging cervids, and the disease is likely to continue to spread geographically [10]. However, the potential that white-tailed deer may be susceptible to sheep scrapie by a natural route presents an additional confounding factor to halting the spread of CWD. This leads to the additional speculations that
1) infected deer could serve as a reservoir to infect sheep with scrapie offering challenges to scrapie eradication efforts and
2) CWD spread need not remain geographically confined to current endemic areas, but could occur anywhere that sheep with scrapie and susceptible cervids cohabitate.
This work demonstrates for the first time that white-tailed deer are susceptible to sheep scrapie by intracerebral inoculation with a high attack rate and that the disease that results has similarities to CWD.
These experiments will be repeated with a more natural route of inoculation to determine the likelihood of the potential transmission of sheep scrapie to white-tailed deer. If scrapie were to occur in white-tailed deer, results of this study indicate that it would be detected as a TSE, but may be difficult to differentiate from CWD without in-depth biochemical analysis.
2012 PO-039: A comparison of scrapie and chronic wasting disease in white-tailed deer
Justin Greenlee, Jodi Smith, Eric Nicholson US Dept. Agriculture; Agricultural Research Service, National Animal Disease Center; Ames, IA USA
snip...
The results of this study suggest that there are many similarities in the manifestation of CWD and scrapie in WTD after IC inoculation including early and widespread presence of PrPSc in lymphoid tissues, clinical signs of depression and weight loss progressing to wasting, and an incubation time of 21-23 months.
Moreover, western blots (WB) done on brain material from the obex region have a molecular profile similar to CWD and distinct from tissues of the cerebrum or the scrapie inoculum. However, results of microscopic and IHC examination indicate that there are differences between the lesions expected in CWD and those that occur in deer with scrapie: amyloid plaques were not noted in any sections of brain examined from these deer and the pattern of immunoreactivity by IHC was diffuse rather than plaque-like.
*** After a natural route of exposure, 100% of WTD were susceptible to scrapie.
Deer developed clinical signs of wasting and mental depression and were necropsied from 28 to 33 months PI. Tissues from these deer were positive for PrPSc by IHC and WB.
Similar to IC inoculated deer, samples from these deer exhibited two different molecular profiles: samples from obex resembled CWD whereas those from cerebrum were similar to the original scrapie inoculum. On further examination by WB using a panel of antibodies, the tissues from deer with scrapie exhibit properties differing from tissues either from sheep with scrapie or WTD with CWD. Samples from WTD with CWD or sheep with scrapie are strongly immunoreactive when probed with mAb P4, however, samples from WTD with scrapie are only weakly immunoreactive. In contrast, when probed with mAb’s 6H4 or SAF 84, samples from sheep with scrapie and WTD with CWD are weakly immunoreactive and samples from WTD with scrapie are strongly positive.
This work demonstrates that WTD are highly susceptible to sheep scrapie, but on first passage, scrapie in WTD is differentiable from CWD.
COLORADO THE ORIGIN OF CHRONIC WASTING DISEASE CWD TSE PRION? *** Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep. IN CONFIDENCE, REPORT OF AN UNCONVENTIONAL SLOW VIRUS DISEASE IN ANIMALS IN THE USA 1989
ALSO, one of the most, if not the most top TSE Prion God in Science today is Professor Adriano Aguzzi, and he recently commented on just this, on a cwd post on my facebook page August 20 at 1:44pm, quote; ''it pains me to no end to even comtemplate the possibility, but it seems entirely plausible that CWD originated from scientist-made spread of scrapie from sheep to deer in the colorado research facility. If true, a terrible burden for those involved.'' August 20 at 1:44pm ...end
cwd scrapie pigs oral routes
***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***
>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***
***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%).
***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.
WEDNESDAY, MAY 29, 2019
***> Incomplete inactivation of atypical scrapie following recommended autoclave decontamination procedures
THURSDAY, DECEMBER 31, 2020
Autoclave treatment of the classical scrapie agent US No. 13-7 and experimental inoculation to susceptible VRQ/ARQ sheep via the oral route results in decreased transmission efficiency
2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains
PLEASE NOTE;
2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains
Olivier Andreoletti, INRA Research Director, Institut National de la Recherche Agronomique (INRA) – École Nationale Vétérinaire de Toulouse (ENVT), invited speaker, presented the results of two recently published scientific articles of interest, of which he is co-author: ‘Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice’ (MarinMoreno et al., 2020) and ‘The emergence of classical BSE from atypical/Nor98 scrapie’ (Huor et al., 2019).
In the first experimental study, H-type and L-type BSE were inoculated into transgenic mice expressing all three genotypes of the human PRNP at codon 129 and into adapted into ARQ and VRQ transgenic sheep mice. The results showed the alterations of the capacities to cross the human barrier species (mouse model) and emergence of sporadic CJD agents in Hu PrP expressing mice: type 2 sCJD in homozygous TgVal129 VRQ-passaged L-BSE, and type 1 sCJD in homozygous TgVal 129 and TgMet129 VRQ-passaged H-BSE.
THURSDAY, SEPTEMBER 24, 2020
The emergence of classical BSE from atypical/ Nor98 scrapie
FRIDAY, OCTOBER 30, 2020
Efficient transmission of US scrapie agent by intralingual route to genetically susceptible sheep with a low dose inoculum
SUNDAY, OCTOBER 11, 2020
Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ
WEDNESDAY, JULY 31, 2019
The agent of transmissible mink encephalopathy passaged in sheep is similar to BSE-L
MONDAY, JULY 27, 2020
APHIS USDA Nor98-like scrapie was confirmed in a sheep sampled at slaughter in May 2020
WEDNESDAY, OCTOBER 28, 2020
***> EFSA Annual report of the Scientific Network on BSE-TSE 2020 Singeltary Submission
SUNDAY, OCTOBER 11, 2020
Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;
A REVIEW of facts and science on scrapie zoonosis potential/likelihood and the USA incredible failure of the BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham)
***> 1st up BSE 589.2001 FEED REGULATIONS
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT
PLOS ONE Journal
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure
Terry S. Singeltary Sr., 03 Jul 2015 at 16:53 GMT
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.
*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***
WEDNESDAY, DECEMBER 23, 2020
Idiopathic Brainstem Neuronal Chromatolysis IBNC BSE TSE Prion a Review 2020
***Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle.
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.
***Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle.
P-088 Transmission of experimental CH1641-like scrapie to bovine PrP overexpression mice
Kohtaro Miyazawa1, Kentaro Masujin1, Hiroyuki Okada1, Yuichi Matsuura1, Takashi Yokoyama2
1Influenza and Prion Disease Research Center, National Institute of Animal Health, NARO, Japan; 2Department of Planning and General Administration, National Institute of Animal Health, NARO
Introduction: Scrapie is a prion disease in sheep and goats. CH1641-lke scrapie is characterized by a lower molecular mass of the unglycosylated form of abnormal prion protein (PrpSc) compared to that of classical scrapie. It is worthy of attention because of the biochemical similarities of the Prpsc from CH1641-like and BSE affected sheep. We have reported that experimental CH1641-like scrapie is transmissible to bovine PrP overexpression (TgBoPrP) mice (Yokoyama et al. 2010). We report here the further details of this transmission study and compare the biological and biochemical properties to those of classical scrapie affected TgBoPrP mice.
Methods: The details of sheep brain homogenates used in this study are described in our previous report (Yokoyama et al. 2010). TgBoPrP mice were intracerebrally inoculated with a 10% brain homogenate of each scrapie strain. The brains of mice were subjected to histopathological and biochemical analyses.
Results: Prpsc banding pattern of CH1641-like scrapie affected TgBoPrP mice was similar to that of classical scrapie affected mice. Mean survival period of CH1641-like scrapie affected TgBoPrP mice was 170 days at the 3rd passage and it was significantly shorter than that of classical scrapie affected mice (439 days). Lesion profiles and Prpsc distributions in the brains also differed between CH1641-like and classical scrapie affected mice.
Conclusion: We succeeded in stable transmission of CH1641-like scrapie to TgBoPrP mice. Our transmission study demonstrates that CH 1641-like scrapie is likely to be more virulent than classical scrapie in cattle.
snip...
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.
CH1641
WEDNESDAY, JULY 31, 2019
The agent of transmissible mink encephalopathy passaged in sheep is similar to BSE-L
49. The agent of transmissible mink encephalopathy passaged in sheep is similar to BSE-L
E. D. Cassmanna,b, S. J. Moorea,b, R. D. Kokemullera, A. Balkema-Buschmannc, M. H. Groschupcand J. J. Greenleea
aVirus and Prion Research Unit, National Animal Disease Center, ARS, United States Department of Agriculture, Ames, IA, USA (EDC, SJM, RDK, JJG); bOak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the U.S. Department of Agriculture (USDA). ORISE is managed by ORAU under DOE contract number DE-SC0014664. (EDC, SJM), Department of Veterinary Pathology, Iowa State University, Ames, IA, USA (JDS); cInstitute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald – Isle of Riems, Germany (ABB, MHG)
CONTACT E. D. Cassmann eric.cassmann@usda.gov
ABSTRACT
Introduction: Transmissible mink encephalopathy (TME) is a fatal neurologic prion disease of farmed mink. Epidemiologic and experimental evidence following a Wisconsin outbreak in 1985 has linked TME to low-type bovine spongiform encephalopathy (BSE-L). Evidence suggests that farmed mink were likely exposed through feeding of BSE-L infected downer cattle. The interspecies transmission of TME to cattle has been documented. Recently, we demonstrated the susceptibility of sheep to cattle passaged TME by intracranial inoculation. The aim of the present study was to compare ovine passaged cattle TME to other prion diseases of food-producing animals. Using a bovine transgenic mouse model, we compared the disease phenotype of sheep TME to BSE-C and BSE-L.
Materials and Methods: Separate inoculants of sheep passaged TME were derived from animals with the VRQ/VRQ (VV136) and ARQ/VRQ (AV136) prion protein genotype. Transgenic bovinized mice (TgBovXV) were intracranially inoculated with 20 µl of 1% w/v brain homogenate. The disease phenotypes were characterized by comparing the attack rates, incubation periods, and vacuolation profiles in TgBovXV mice.
Results: The attack rate for BSE-C (13/13), BSE-L (18/18), and TMEVV (21/21) was 100%; whereas, the TMEAV group (15/19) had an incomplete attack rate. The average incubation periods were 299, 280, 310, and 541 days, respectively. The vacuolation profiles of BSE-L and TMEVV were most similar with mild differences observed in the thalamus and medulla. Vacuolation profiles from the BSE-C and TMEAV experimental groups were different than TMEVVand BSE-L.
Conclusion: Overall the phenotype of disease in TME inoculated transgenic mice was dependent on the sheep donor genotype (VV vs AV). The results of the present study indicate that TME isolated from VRQ/VRQ sheep is similar to BSE-L with regards to incubation period, attack rate, and vacuolation profile. Our findings are in agreement with previous research that found phenotypic similarities between BSE-L and cattle passaged TME in an ovine transgenic rodent model. In this study, the similarities between ovine TME and BSE-L are maintained after multiple interspecies passages.
Prion2019 Conference
2007
August 1988
Evidence That Transmissible Mink Encephalopathy Results From Feeding Infected Cattle
Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME. snip... The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
doi:10.1016/S0021-9975(97)80022-9 Copyright © 1997 Published by Elsevier Ltd.
Second passage of a US scrapie agent in cattle
R.C. Cutlip, J.M. Miller and H.D. Lehmkuhl
United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Ames, Iowa, USA
Received 10 September 1996; accepted 31 July 1997. Available online 25 May 2006.
Summary
Scrapie and bovine spongiform encephalopathy are similar chronic neurodegenerative diseases of sheep and cattle. An earlier study showed that, on first passage in cattle, a US scrapie agent caused an encephalopathy that was distinct from bovine spongiform encephalopathy (BSE). The present report describes a second passage in cattle, carried out because diseases caused by the spongiform encephalopathy agents often change in character with additional passages in abnormal hosts. For this work, young calves were inoculated intracerebrally with a pooled suspension of brain from cattle that had died of encephalopathy after experimental inoculation with brain from scrapie-affected sheep. The second passage disease was essentially identical with the first passage disease, as judged by clinical signs, histopathological findings and distribution of "prion protein scrapie" (PrPsc). This represents additional evidence to suggest that the US sheep scrapie agent tested is incapable of causing BSE in cattle.
(b) the epidemiological and laboratory studies in the USA suggest the possibility of an occurrence of BSE infection in cattle as the origin of outbreaks of TME.
{c) there is also evidence from two experiments conducted in the USA that cattle, though susceptible to scrapie inocula prepared from sheep, express a pathology quite different from that of BSE and not convincingly diagnostic of an SE by histopathological criteria. Furthermore, neither of these studies can be regarded as a basis for extrapolation to the situation in the UK because the inocula used were either experimentally passaged or natural scrapie originating from Suffolk sheep; a minority breed in this country.
Is There a Scrapie-Like Disease in Cattle? R.F. Marsh*, DVM, PhD and G.R. Hartsough, DVM
Transmissible mink encephalopathy (TME) is a rare disease of ranch-reared mink which is indistinguishable from sheep scrapie. Previous studies on the epidemiology of TME have not identified a definite source of infection for mink. Studies on experimental transmission have shown that mink are susceptible to intracerebral inoculation of American Suffolk scrapie, but that the incubation periods are longer (>1 year) than those observed in natural outbreaks of TME (<1 year).
In April of 1985, a mink rancher in Wisconsin reported a debilitating neurologic disease in his herd which we diagnosed as TME by histopathologic findings confirmed by experimental transmission to mink and squirrel monkeys. The rancher was a “dead stock" feeder using mostly (>95%) downer or dead dairy cattle and a few horses. Sheep had never been fed.
We believe that these findings may indicate the presence of a previously unrecognized scrapie-like disease in cattle and wish to alert dairy practitioners to this possibility.
* Department of Veterinary Science, University of Wisconsin-
- Madison, Madison, WI 53706, .
* Director of the GLMA/EMBA Ranch Service, P.0. Box 342, Thiensville, WI 53092.
PROCEEDINGS OF THE SEVENTH ANNUAL WESTERN CONFERENCE FOR FOOD ANIMAL VETERINARY MEDICINE, University of Arizona, March 17-19, 1986
August 1988
Evidence That Transmissible Mink Encephalopathy Results From Feeding Infected Cattle
Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME. snip... The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
SUNDAY, OCTOBER 4, 2020
Cattle Meat and Offal Imported from the United States of America, Canada and Ireland to Japan (Prions) Food Safety Commission of Japan
SEE HADLOW AND SCRAPIE !
Monday, December 1, 2008
When Atypical Scrapie cross species barriers
Authors
Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.
Content
Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.
The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.
Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.
Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.
(i) the unsuspected potential abilities of atypical scrapie to cross species barriers
(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier
These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.
Neuroprion 2008 Abstract Book
WEDNESDAY, JUNE 10, 2020
Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice
Atypical BSE prions showed a modification in their zoonotic ability after adaptation to sheep-PrP producing agents able to infect TgMet129 and TgVal129, bearing features that make them indistinguishable of sporadic Creutzfeldt-Jakob disease prions.
our results clearly indicate that atypical BSE adaptation to an ovine-PrP sequence could modify the prion agent to potentially infect humans, showing strain features indistinguishable from those of classic sCJD prions, even though they might or might not be different agents.
However, the expanding range of TSE agents displaying the capacity to transmit in human-PrP–expressing hosts warrants the continuation of the ban on meat and bone meal recycling and underscores the ongoing need for active surveillance
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
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, Valerie 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 long 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***
===============
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
==============
Prion 2015 Conference Abstract Book
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
Title: Transmission of scrapie prions to primate after an extended silent incubation period)
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
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).
THURSDAY, JANUARY 7, 2021
Atypical Nor-98 Scrapie TSE Prion USA State by State Update January 2021
P03.141
Aspects of the Cerebellar Neuropathology in Nor98
Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,
Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.
Prion Conference 2007 Abstract Book
PR-26
NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS
R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway
Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as "atypical" scrapie, as opposed to "classical scrapie". Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion.
*** Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.
119
Neuroprion 2006 Conference Abstract Book
A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes
Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,? +Author Affiliations
*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway
***Edited by Stanley B. Prusiner, University of California, San Francisco, CA (received for review March 21, 2005)
Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. *** These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.
WEDNESDAY, NOVEMBER 20, 2019
Review: Update on Classical and Atypical Scrapie in Sheep and Goats
FRIDAY, FEBRUARY 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
SEE HADLOW AND SCRAPIE !
WEDNESDAY, JUNE 10, 2020
Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice
Atypical BSE prions showed a modification in their zoonotic ability after adaptation to sheep-PrP producing agents able to infect TgMet129 and TgVal129, bearing features that make them indistinguishable of sporadic Creutzfeldt-Jakob disease prions.
our results clearly indicate that atypical BSE adaptation to an ovine-PrP sequence could modify the prion agent to potentially infect humans, showing strain features indistinguishable from those of classic sCJD prions, even though they might or might not be different agents.
However, the expanding range of TSE agents displaying the capacity to transmit in human-PrP–expressing hosts warrants the continuation of the ban on meat and bone meal recycling and underscores the ongoing need for active surveillance
FRIDAY, OCTOBER 23, 2020
Scrapie TSE Prion Zoonosis Zoonotic, what if?
FRIDAY, FEBRUARY 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains
PLEASE NOTE;
2.3.2. New evidence on the zoonotic potential of atypical BSE and atypical scrapie prion strains
Olivier Andreoletti, INRA Research Director, Institut National de la Recherche Agronomique (INRA) – École Nationale Vétérinaire de Toulouse (ENVT), invited speaker, presented the results of two recently published scientific articles of interest, of which he is co-author: ‘Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice’ (MarinMoreno et al., 2020) and ‘The emergence of classical BSE from atypical/Nor98 scrapie’ (Huor et al., 2019).
In the first experimental study, H-type and L-type BSE were inoculated into transgenic mice expressing all three genotypes of the human PRNP at codon 129 and into adapted into ARQ and VRQ transgenic sheep mice. The results showed the alterations of the capacities to cross the human barrier species (mouse model) and emergence of sporadic CJD agents in Hu PrP expressing mice: type 2 sCJD in homozygous TgVal129 VRQ-passaged L-BSE, and type 1 sCJD in homozygous TgVal 129 and TgMet129 VRQ-passaged H-BSE.
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
FRIDAY, OCTOBER 23, 2020
Scrapie TSE Prion Zoonosis Zoonotic, what if?
TUESDAY, SEPTEMBER 22, 2020
APHIS USDA MORE SCRAPIE ATYPICAL Nor-98 Confirmed USA September 15 2020
Personal Communication from USDA et al Mon, Jan 4, 2021 11:37 am...terry
17 cases of the Nor98 in the USA to date
17 Nor98-like cases since the beginning of RSSS.
TUESDAY, JANUARY 12, 2021
Annual Scrapie Report Available for Fiscal Year 2020 USA October 1, 2019 to September 30, 2020
THURSDAY, JANUARY 7, 2021
Atypical Nor-98 Scrapie TSE Prion USA State by State Update January 2021
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. | 4:38 PM
0 Comments:
Post a Comment
Subscribe to Post Comments [Atom]
<< Home