Evidence of effective scrapie transmission via colostrum and milk in sheep
Evidence of effective scrapie transmission via colostrum and milk in sheep
BMC Veterinary Research 2013, 9:99 doi:10.1186/1746-6148-9-99
Timm Konold (Timm.Konold@ahvla.gsi.gov.uk) S Jo Moore
(J.Moore@murdoch.edu.au) Susan J Bellworthy (susanjbellworthy@btinternet.com)
Linda A Terry (lindaannterry@gmail.com) Leigh Thorne
(Leigh.Thorne@ahvla.gsi.gov.uk) Andrew Ramsay (Andrew.Ramsay@ahvla.gsi.gov.uk) F
Javier Salguero (Javier.Salguero@ahvla.gsi.gov.uk) Marion M Simmons
(Marion.Simmons@ahvla.gsi.gov.uk) Hugh A Simmons (Hugh.Simmons@ahvla.gsi.gov.uk)
ISSN 1746-6148 Article type Research article Submission date 21 February
2013 Acceptance date 30 April 2013 Publication date 7 May 2013 Article URL http://www.biomedcentral.com/1746-6148/9/99
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Evidence of effective scrapie transmission via colostrum and milk in sheep
Timm Konold1* * Corresponding author Email: Timm.Konold@ahvla.gsi.gov.uk S
Jo Moore2,3 Email: J.Moore@murdoch.edu.au Susan J Bellworthy2 Email:
susanjbellworthy@btinternet.com Linda A Terry2 Email: lindaannterry@gmail.com
Leigh Thorne4 Email: Leigh.Thorne@ahvla.gsi.gov.uk Andrew Ramsay4 Email:
Andrew.Ramsay@ahvla.gsi.gov.uk F Javier Salguero1 Email:
Javier.Salguero@ahvla.gsi.gov.uk Marion M Simmons1 Email:
Marion.Simmons@ahvla.gsi.gov.uk Hugh A Simmons1 Email:
Hugh.Simmons@ahvla.gsi.gov.uk
1 Specialist Scientific Support Department, Animal Health and Veterinary
Laboratories Agency Weybridge, New Haw Addlestone, Surrey KT15 3NB, UK
2 Formerly – Veterinary Laboratories Agency Weybridge, New Haw, Addlestone,
Surrey KT15 3NB, UK
3 School of Veterinary and Biomedical Sciences, Murdoch University, South
Street, Murdoch, WA 6150, Australia
4 TSE Department, Animal Health and Veterinary Laboratories Agency, New
Haw, Addlestone, Surrey KT15 3NB, UK
Abstract
Background
Evidence for scrapie transmission from VRQ/VRQ ewes to lambs via milk was
first reported in 2008 but in that study there were concerns that lateral
transmission may have contributed to the high transmission rate observed since
five control lambs housed with the milk recipients also became infected. This
report provides further information obtained from two follow-up studies, one
where milk recipients were housed separately after milk consumption to confirm
the validity of the high scrapie transmission rate via milk and the second to
assess any difference in infectivity from colostrum and subsequent milk. Protein
misfolding cyclic amplification (PMCA) was also used to detect prion protein in
milk samples as a comparison with the infectivity data and extended to milk
samples from ewes without a VRQ allele.
Results
Seven pairs of lambs fed colostrum and milk individually from seven
scrapie-affected sheep (pre-clinical or clinical) presented with
disease-associated prion protein, PrPd, in rectal lymphoid tissue at 4–5 months
of age. Five further pairs of lambs fed either colostrum or subsequent milk from
five pre-clinical scrapie-affected sheep equally presented with PrPd in lymphoid
tissue by 9 months of age. Nine sheep were lost due to intercurrent diseases but
all remaining milk or colostrum recipients, including those in the original
study with the lateral transmission controls, developed clinical signs of
scrapie from 19 months of age and scrapie was confirmed by brain examination.
Unexposed control sheep totalling 19 across all three studies showed no evidence
of infection.
Scrapie PrP was amplified repeatedly by PMCA in all tested milk samples
from scrapieaffected VRQ/VRQ sheep, and in one scrapie-affected ARQ/ARQ sheep.
By contrast, milk
samples from five VRQ/VRQ and 11 ARQ/ARQ scrapie-free sheep did not have
detectable scrapie PrP on repeated tests.
Conclusions
Feeding of milk from scrapie-affected sheep results in a high transmission
rate in VRQ/VRQ sheep and both colostrum and milk transmit scrapie. Detection of
scrapie prion protein in individual milk samples from scrapie-affected ewes
confirms PMCA as a valuable in vitro test.
Keywords
Transmissible spongiform encephalopathy, Scrapie, Sheep, Milk, Colostrum,
Transmission, PMCA, Prion protein, RAMALT, Copper
Tuesday, April 30, 2013 Transmission of classical scrapie via goat milk
Veterinary Record2013;172:455 doi:10.1136/vr.f2613
Letters
Ruminant Health
Transmission of classical scrapie via goat milk
Timm Konold1, Hugh A. Simmons1, Paul R. Webb1, Peter J. Bellerby1, Steve A.
C. Hawkins1 and Lorenzo González2
+ Author Affiliations
1AHVLA – Weybridge, New Haw, Addlestone, Surrey KT15 3NB 2– Lasswade,
Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ e-mail:
timm.konold@ahvla.gsi.gov.uk
FOLLOWING reports that ovine scrapie (referred to here and subsequently as
classical scrapie) can be transmitted from dams to lambs via milk (Konold and
others 2008, Ligios and others 2011), we subsequently carried out a study to
investigate whether caprine scrapie could also be transmitted via milk, using
material collected from a field outbreak of scrapie in goats in the UK (González
and others 2009). Lambs were selected as milk recipients from a closed flock of
known scrapie-free status (Simmons and others 2009) because an assured
scrapie-free source of goats was not available.
Due to the lack of published information about the susceptibility of sheep
to caprine scrapie, a pilot study was conducted to determine whether sheep were
susceptible to …
snip...
The study is still ongoing but the current results confirm that the
scrapie agent can also be transmitted via milk from goats. This reinforces the
validity of the decision by the European Parliament in 2009 to prohibit the
feeding of milk or milk products from classical scrapie-infected flocks or herds
to small ruminants in general.
Timm Konold, Hugh A. Simmons,
please see full text @
Sunday, February 10, 2013
Scientific Opinion on the risk of transmission of classical scrapie via in
vivo derived embryo transfer in ovine animals
Saturday, February 11, 2012
PrPSc Detection and Infectivity in Semen from Scrapie-Infected Sheep
Wednesday, January 18, 2012
BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE
February 1, 2012
Envt.18: Mother to Offspring Transmission of Chronic Wasting Disease
Candace K. Mathiason,† Amy Nalls, Kelly Anderson, Jeanette Hayes-Klug,
Jenny G. Powers, Nicholas J. Haley and Edward A. Hoover
Colorado State University; Fort Collins, CO USA†Presenting author; Email:
ckm@lamar.colostate.edu
We have developed a new cervid model in small Asian muntjac deer (Muntiacus
reevesi) to study potential modes of vertical transmission of chronic wasting
disease (CWD) from mother to offspring. Eight of eight (8/8) muntjac doe orally
infected with CWD tested PrPCWD lymphoid positive by four months post infection.
Ten fawns were born to these CWD-infected doe— four of the fawns were viable,
five were non-viable and one was a first trimester fetus harvested from a
CWD-infected doe euthanized at end-stage disease. The viable fawns have been
monitored for CWD infection by immunohistochemistry and sPMCA performed on
serial tonsil and rectal lymphoid tissue biopsies. PrPCWD has been detected in
one fawn by IHC as early as 40 days of age. Moreover, sPMCA performed on rectal
lymphoid tissue has yielded positive results on another fawn at ten days of age.
In addition, sPMCA assays have demonstrated amplifiable prions in fetal
placental or spleen tissue of three non-viable fawns and mammary tissue of the
dams.
Additional pregnancy related fluids and tissues from the doe as well as
tissue from the nonviable fawns are currently being probed for the presence of
CWD. In summary, we have employed the muntjac deer model, to demonstrate for the
first time the transmission of CWD from mother to offspring. These studies
provide the foundation to investigate the mechanisms and pathways of maternal
prion transfer.
===========================
PPo3-18: A Possible Case of Maternal Transmission of the BSE Agent within
Captive Cheetah Affected with Feline Spongiform Encephalopathy
Anna Bencsik, Sabine Debeer, Thierry Petit and Thierry Baron
Afssa; Unité ATNC; Lyon, France; Zoo de la Palmyre; Les Mathes, France
Key words: BSE, FSE, vertical transmission
Introduction. Feline spongiform encephalopathy (FSE) is considered to be
related to bovine spongiform encephalopathy (BSE). It has been reported in
domestic cats as well as in captive wild cats including cheetahs, first in the
United Kingdom (UK) and then in other European countries. In France, several
cases were described in cheetahs either imported from UK or born in France. Here
we report details of two other FSE cases in captive cheetah. These cases are of
particular interest since the 2nd case of FSE in a cheetah born in France,
appears most likely due to maternal transmission.1
Results. Complete PrPd study showed the close likeness between the two
cheetah cases. The TgOvPrP4 mouse brains infected with cattle BSE and cheetah
FSE revealed similar vacuolar lesion profiles, PrPd brain mapping with
occurrence of typical florid plaques.
Materials and Methods. Using immunohistochemistry (IHC), pathological form
of PrP(PrPd) was analyzed in the brains and peripheral organs of these two
cheetahs. Transmission studies to the TgOvPrP4 mouse line were also performed,
for comparison with the transmission of cattle BSE. Lesion profiles of the
infected transgenic mice were analyzed as well as type and brain distribution of
PrPd.
Conclusion. Collectively, these data indicate that both FSE cases harbor
the same strain of agent as the cattle BSE agent. Because this is most probably
a case of maternal transmission of the disease, this new observation may have
some impact on our knowledge of vertical transmission of BSE agent-linked TSEs
such as in human variant Creutzfeldt Jakob disease.
References
1. Bencsik et al. PLoS One 2009; 4:6929.
=========================
PPo3-40: Mother to Offspring Transmission of Chronic Wasting Disease
Candace K. Mathiason, Amy V. Nalls, Kelly Anderson, Jeanette Hayes-Klug,
Nicholas Haley and Edward A. Hoover
Colorado State University, Department of Microbiology, Immunology and
Pathology, Fort Collins, CO USA
Key words: Chronic wasting disease, vertical transmission, muntjac deer
We have developed a new cervid model in small Asian muntjac deer (Muntiacus
reevesi) to study potential modes of vertical transmission of chronic wasting
disease (CWD) from mother to offspring. Eight of eight (8/8) muntjac doe orally
infected with CWD tested PrPCWD lymphoid positive by 4 months post infection.
Six fawns were born to these CWD-infected doe. Six fawns were born to 6
CWD-infected doe; 4 of the fawns were non-viable. The viable fawns have been
monitored for CWD infection by immunohistochemistry and sPMCA performed on
serial tonsil and rectal lymphoid tissue biopsies. PrPCWD has been detected in
one fawn as early as 40 days of age. Moreover, sPMCA performed on rectal
lymphoid tissue has yield positive results on another fawn at 10 days of age. In
addition, sPMCA assays have also demonstrated amplifiable prions in maternal
placental (caruncule) and mammary tissue of the dam.
Additional pregnancy related fluids and tissues from the doe as well as
tissue from the nonviable fawns are currently being probed for the presence of
CWD. In summary, we have employed the muntjac deer model, to demonstrate for the
first time the transmission of CWD from mother to offspring. These studies
provide the foundation to investigate the mechanisms and pathways of maternal
prion transfer.
PRION 2011
landesbioscience.com
International Prion Congress: From agent to diseaseSeptember 8–11,
2010Salzburg, Austria
Saturday, December 3, 2011
Isolation of Prion with BSE Properties from Farmed Goat Volume 17, Number
12—December 2011
PRION 2010
Friday, December 23, 2011
Detection of PrPres in Genetically Susceptible Fetuses from Sheep with
Natural Scrapie
Monday, November 22, 2010
SHEEP WITH MASTITIS TRANSMIT INFECTIOUS PRIONS THROUGH THE MILK http://scrapie-usa.blogspot.com/2010/11/sheep-with-mastitis-transmit-infectious.html
Saturday, April 12, 2008
Evidence of scrapie transmission via milk
Wednesday, January 18, 2012
Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural
Scrapie Isolates Similar to CH1641 Experimental Scrapie
Journal of Neuropathology & Experimental Neurology: February 2012 -
Volume 71 - Issue 2 - p 140–147
Wednesday, February 16, 2011
IN CONFIDENCE
SCRAPIE TRANSMISSION TO CHIMPANZEES
IN CONFIDENCE
Sunday, December 12, 2010
EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2
December 2010
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
Thursday, December 23, 2010
Molecular Typing of Protease-Resistant Prion Protein in Transmissible
Spongiform Encephalopathies of Small Ruminants, France, 2002-2009
Volume 17, Number 1 January 2011
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform
encephalopathy following passage in sheep
Monday, April 25, 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Volume 17, Number 5-May 2011
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
Thursday, March 29, 2012
atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
NIAA Annual Conference April 11-14, 2011San Antonio, Texas
Wednesday, April 4, 2012
20120402 - Breach of quarantine/Violation de la mise en quarantaine of an
ongoing Scrapie investigation
Michigan and California have had a high spike in Goat Scrapie cases,
compared to elsewhere ???
Tuesday, February 01, 2011
Sparse PrP-Sc accumulation in the placentas of goats with naturally
acquired scrapie
(Figure 6) including five goat cases in FY 2008 that originated from the
same herd in Michigan. This is highly unusual for goats, and I strenuously urge
that there should be an independent investigation into finding the common
denominator for these 5 goats in the same herd in Michigan with Scrapie. ...
Thursday, February 23, 2012
Atypical Scrapie NOR-98 confirmed Alberta Canada sheep January 2012
RESEARCH
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 5, May 2011
Experimental Oral Transmission of Atypical Scrapie to Sheep
Marion M. Simmons, S. Jo Moore,1 Timm Konold, Lisa Thurston, Linda A.
Terry, Leigh Thorne, Richard Lockey, Chris Vickery, Stephen A.C. Hawkins,
Melanie J. Chaplin, and John Spiropoulos
To investigate the possibility of oral transmission of atypical scrapie in
sheep and determine the distribution of infectivity in the animals’ peripheral
tissues, we challenged neonatal lambs orally with atypical scrapie; they were
then killed at 12 or 24 months. Screening test results were negative for
disease-specifi c prion protein in all but 2 recipients; they had positive
results for examination of brain, but negative for peripheral tissues.
Infectivity of brain, distal ileum, and spleen from all animals was assessed in
mouse bioassays; positive results were obtained from tissues that had negative
results on screening. These fi ndings demonstrate that atypical scrapie can be
transmitted orally and indicate that it has the potential for natural
transmission and iatrogenic spread through animal feed. Detection of infectivity
in tissues negative by current surveillance methods indicates that diagnostic
sensitivity is suboptimal for atypical scrapie, and potentially infectious
material may be able to pass into the human food chain.
SNIP...
Although we do not have epidemiologic evidence that supports the effi cient
spread of disease in the fi eld, these data imply that disease is potentially
transmissible under fi eld situations and that spread through animal feed may be
possible if the current feed restrictions were to be relaxed. Additionally,
almost no data are available on the potential for atypical scrapie to transmit
to other food animal species, certainly by the oral route. However, work with
transgenic mice has demonstrated the potential susceptibility of pigs, with the
disturbing fi nding that the biochemical properties of the resulting PrPSc have
changed on transmission (40). The implications of this observation for
subsequent transmission and host target range are currently unknown.
How reassuring is this absence of detectable PrPSc from a public health
perspective? The bioassays performed in this study are not titrations, so the
infectious load of the positive gut tissues cannot be quantifi ed, although
infectivity has been shown unequivocally. No experimental data are currently
available on the zoonotic potential of atypical scrapie, either through
experimental challenge of humanized mice or any meaningful epidemiologic
correlation with human forms of TSE. However, the detection of infectivity in
the distal ileum of animals as young as 12 months, in which all the tissues
tested were negative for PrPSc by the currently available screening and confi
rmatory diagnostic tests, indicates that the diagnostic sensitivity of current
surveillance methods is suboptimal for detecting atypical scrapie and that
potentially infectious material may be able to pass into the human food chain
undetected.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 5, May 2011
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely
create alarm in some circles even if the result could not be interpreted for
man. I have a view that all these agents could be transmitted provided a large
enough dose by appropriate routes was given and the animals kept long enough.
Until the mechanisms of the species barrier are more clearly understood it might
be best to retain that hypothesis.
snip...
R. BRADLEY
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to
nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep
and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were
exposed to the infectious agents only by their nonforced consumption of known
infectious tissues. The asymptomatic incubation period in the one monkey exposed
to the virus of kuru was 36 months; that in the two monkeys exposed to the virus
of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the
two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively.
Careful physical examination of the buccal cavities of all of the monkeys failed
to reveal signs or oral lesions. One additional monkey similarly exposed to kuru
has remained asymptomatic during the 39 months that it has been under
observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie
by natural feeding to squirrel monkeys that we have reported provides further
grounds for concern that scrapie-infected meat may occasionally give rise in
humans to Creutzfeldt-Jakob disease.
PMID: 6997404
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, December 20, 2012
OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED AND SAME OLD BSe
WITH BOVINE MAD COW DISEASE
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH
CODE
Wednesday, April 24, 2013
Chimpanzees Released After 30 Years Of Testing, Brace Yourself For Smiles
THE OIE, USDA, CFIA, DEFRA, MAFF, $$$ POLICY OF SPREADING THE TSE PRION
DISEASE GLOBALLY, THE LEGAL TRADING OF ATYPICAL AND POSSIBLY TYPICAL SCRAPIE AS
A COMMODITY. ...
absolutely insane, crazy, absurd, NEGLIGENT, take your pick. ...
Tuesday, April 30, 2013
Transmission of classical scrapie via goat milk
Veterinary Record2013;172:455 doi:10.1136/vr.f2613
TSS
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