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From: TSS (216-119-162-72.ipset44.wt.net)
Subject: Re: TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES (Williams et al) (rebuttal, TSS et me;-)
Date: March 6, 2003 at 11:09 am PST
In Reply to: TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES (Williams et al) (rebuttal, TSS et me;-) posted by TSS on March 6, 2003 at 9:47 am:
>>>Many species are experimentally susceptible to
CWD by intracerebral inoculation, an unnatural but
commonly used route for the study of prion disease.
Mink, domestic ferret Mustela putorius furo, squirrel
monkey Saimiri sciureus, mule deer, domestic goat
(Williams and Young 1992), and laboratory mice
(Bruce et al. 1997) are susceptible to CWD by this
route on primary passage.<<< hmmm, unless i missed it, i think 2 things need to
be said; 1st, and most recently (2002), a 4th cow went down
by this mode of experimental transmission. this
is very important. could it not be that the experimental
mode of transmission via inoculation, has a shorter
incubation period than the mode by natural oral route? 2nd, scrapie and cwd transmit to cattle/primates,
humans are primates. there has __never__ been transmission studies done on humans. Subject: Re: CWD TO CATTLE by inoculation (ok, is it three or four???)
Date: Mon, 25 Nov 2002 10:13:42 -0600
From: "Janice M. Miller"
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de######## Bovine Spongiform Encephalopathy ######### The statement that 4 cattle have developed evidence of CWD transmission
following intracerebral inoculation is correct because an additional
animal has been found prion positive subsequent to the 2001 paper that
presented preliminary findings after only 2 and a half years of
observation. Following this message is a summary of the current status
of our CWD cross-species transmission experiments in cattle and sheep.
This information was prepared in anticipation of questions about these
studies that we expected would be raised at the recent annual meeting of
the U.S. Animal Health Association.
I would like to correct one statement in the newspaper article
that was attributed to me that is in error. I did not imply that our
work thus far could be extrapolated to the situation with white-tailed
deer and dairy cattle. While there is no indication that there should
be any difference in susceptibility of beef versus dairy cattle, we do
not know if the CWD agent in white-tailed deer would be equivalent to
that obtained from mule deer. For that reason Dr. Hamir is now
repeating the original experiment in cattle with brain suspension from
affected white-tails as inoculum. Experimental Transmission of Chronic Wasting Disease (CWD) to Cattle
and Sheep
Progress report - October 15, 2002 Transmission of CWD (mule deer) to cattle: Background:
In 1997, 13 calves were inoculated intracerebrally with brain
suspension from mule deer naturally affected with CWD. During the first
3 years, 3 animals were euthanized 23, 24, and 28 months after
inoculation because of weight loss (2) or sudden death (1). Although
microscopic examination of the brains did not show classical lesions of
transmissible spongiform encephalopathy (TSE), a specific TSE marker
protein, PrPres, was detected by immunohistochemistry (IHC) and western
blot . Detailed information on these animals has been published
previously (A Hamir et al., J Vet Diagn Invest 13: 91-96, 2001). Update:
During the 3rd and 4th years of observation, 5 additional animals have
been euthanized because of health concerns (primarily chronic joint and
foot problems). Although all tests for PrPres are not complete, IHC
results indicate that 1 of these animals, necropsied 59 months after
inoculation, was positive for PrPres. This animal (# 1746) had not been
eating well for approximately 1 week prior to being found recumbent. At
necropsy, significant gross lesions consisted of an oblique fracture of
L1 vertebral arch with extension into the body, and moderate multifocal
hemorrhagic ulceration in the abomasum. Microscopic examination of
brain revealed a few isolated neurons with single or multiple vacuoles,
but neither neuronal degeneration nor gliosis was observed. IHC
revealed the presence of PrPres in sections from several areas of the
brain. Summary of findings on this case and data from previous animals: Necropsy Survival Disease Clinical
Histo- IHC SAF WB
No. Route date period course signs pathology ________________________________________________________________ 1745 i/c 8/18/99 23m 2m +
+/- + - + 1768 i/c 9/22/99 24m 3m +
+/- + + + 1744 i/c 1/29/00 28m 3d +/-
- + + + 1749 i/c 5/20/01 44m NA -
- - NT NT 1748 i/c 6/27/01 45m NA -
- - NT NT 1743 i/c 8/21/02 59m NA -
- - Pending Pending 1741 i/c 8/22/02 59m NA -
- - Pending Pending 1746 i/c 8/27/02 59m 7d +/-
+/- + Pending Pending NT = not tested; IHC = immunohistochemistry for PrPres; SAF = scrapie
associated fibrils; NA = not applicable; WB = Western blot
(Prionics-Check); + = lesions or antigen present; - = lesions or
antigen absent; +/- = signs/lesions equivocal; i/c = intracerebral; m =
months; d = days. Summary:
After 5 years of observation we have 4 CWD transmissions to cattle from
a group of 13 inoculates. These animals, which were necropsied 23, 24,
28, and 59 months after inoculation, did not show the clinical signs or
histopathologic lesions typical of a TSE, but PrPres was detected in
brain samples. Four other animals that were necropsied during the 4th
and 5th years of observation have not shown evidence of prion disease
(although not all tests are complete) and the 5 remaining cattle are
apparently healthy. Note that this study involved direct intracerebral
inoculation of cattle with the CWD agent, which is an unnatural route of
exposure. It is likely that transmission by a more natural route, such
as oral exposure, would be much more difficult to accomplish. Cattle
have been inoculated orally at the University of Wyoming with the same
inoculum used for this experiment, and 5 years into the study these
animals remain healthy.
Experimental Transmission of CWD (mule deer) to sheep
Eight Suffolk sheep from the NADC scrapie-free flock were inoculated
intracerebrally with the CWD brain suspension used to inoculate cattle.
PRNP genotyping showed that 4 of the sheep were QQ at codon 171 and the
other four were QR. Two of the QQ sheep were euthanized during the 3rd
year of observation. At necropsy one of these animals had a urethral
obstruction and PrPres was not detected in brain or lymphoid tissues.
The other sheep, necropsied 35 months after inoculation, showed clinical
signs and histopathologic lesions that were indistinguishable from
scrapie. IHC tests showed typical PrPres accumulations in brain,
tonsil, and some lymph nodes. The 2 remaining QQ sheep and all 4 QR
sheep are apparently healthy 39 months after inoculation. Summary:
After 3 years of observation we have 1 transmission of CWD to a 171 QQ
sheep. This animal, which was necropsied 35 months after inoculation,
showed clinical signs and histopathologic lesions that were
indistinguishable from scrapie. Another QQ sheep that was necropsied
during the 3rd year showed no evidence of prion disease and all
remaining sheep (2 QQ and 4 QR) are apparently healthy. >>> flounder@WT.NET 11/23/02 06:54PM >>>
######## Bovine Spongiform Encephalopathy
#########1: J Vet Diagn Invest 2001 Jan;13(1):91-6 Preliminary findings on the experimental transmission of chronic
wasting
disease agent of mule deer to cattle. Hamir AN, Cutlip RC, Miller JM, Williams ES, Stack MJ, Miller MW,
O'Rourke KI, Chaplin MJ. National Animal Disease Center, ARS, USDA, Ames, IA 50010, USA. To determine the transmissibility of chronic wasting disease (CWD) to
cattle and to provide information about clinical course, lesions, and
suitability of currently used diagnostic procedures for detection of
CWD
in cattle, 13 calves were inoculated intracerebrally with brain
suspension from mule deer naturally affected with CWD. Between 24 and
27
months postinoculation, 3 animals became recumbent and were
euthanized.
Gross necropsies revealed emaciation in 2 animals and a large
pulmonary
abscess in the third. Brains were examined for protease-resistant
prion
protein (PrP(res)) by immunohistochemistry and Western blotting and
for
scrapie-associated fibrils (SAFs) by negative-stain electron
microscopy.
Microscopic lesions in the brain were subtle in 2 animals and absent
in
the third case. However, all 3 animals were positive for PrP(res) by
immunohistochemistry and Western blot, and SAFs were detected in 2 of
the animals. An uninoculated control animal euthanized during the same
period did not have PrP(res) in its brain. These are preliminary
observations from a currently in-progress experiment. Three years
after
the CWD challenge, the 10 remaining inoculated cattle are alive and
apparently healthy. These preliminary findings demonstrate that
diagnostic techniques currently used for bovine spongiform
encephalopathy (BSE) surveillance would also detect CWD in cattle
should
it occur naturally. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11243374&dopt=Abstract
Sat, Nov 23, 2002
Scientists unsure if CWD can jump species By Jessica Bock
Wausau Daily Herald
jbock@wdhprint.com snip... Janice Miller, a veterinarian in charge of the experiment, said she
believes previous research shows it is hard for the disease to be
transmitted naturally from whitetail deer to dairy cattle.
"Our study says nothing of how it could be transmitted in natural
surroundings," she said. Miller has been studying the transmission of CWD from mule deer to
cattle since 1997. Since then, chronic wasting disease was transmitted
to four out of 13 cattle injected with brain tissue from naturally
infected mule deer, she said. In Wyoming, Williams has been studying cattle that were given a
concoction of diseased brain tissue orally, and five years into the
study the animals remain healthy, Miller said.
No one knows if chronic wasting disease could ever spread to another
species through natural surroundings. "Our experience is that it's pretty hard to predict," Miller said. http://www.wausaudailyherald.com/wdhlocal/277564794712612.shtml greetings list, > Since then, chronic wasting disease was > transmitted to four out of 13 cattle is this a typo by the media or has another cow gone down
with CWD since the preliminary findings were found? TSS ########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html
##########
######## 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. PMID: 6997404 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract TSS
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