Sunday, August 19, 2012

Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation 2012

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES Location: Virus and Prion Research Unit
Title: Susceptibility of cattle to the agent of chronic wasting disease from elk after intracranial inoculation
Authors
Greenlee, Justin Nicholson, Eric Smith, Jodi Kunkle, Robert Hamir, Amirali
Submitted to: Journal of Veterinary Diagnostic Investigation Publication Type: Peer Reviewed Journal Publication Acceptance Date: July 12, 2012 Publication Date: N/A
Interpretive Summary: Chronic Wasting Disease (CWD), a fatal neurodegenerative disease that occurs in farmed and wild cervids (deer and elk) of North America, is a transmissible spongiform encephalopathy (TSE). TSEs are caused by infectious proteins called prions that are resistant to various methods of decontamination and environmental degradation. Cattle could be exposed to chronic wasting disease (CWD) by contact with infected farmed or free-ranging cervids. The purpose of this study was to assess the potential transmission of CWD from elk to cattle after intracranial inoculation, the most direct route to test the potential of a host to replicate an isolate of the prion agent. This study reports that only 2 of 14 calves inoculated with CWD from elk had clinical signs or evidence of abnormal prion protein accumulation. These results suggest that cattle are unlikely to be susceptible to CWD if inoculated by a more natural route. This information could have an impact on regulatory officials developing plans to reduce or eliminate TSEs and farmers with concerns about ranging cattle on areas where CWD may be present.
Technical Abstract: Cattle could be exposed to the agent of chronic wasting disease (CWD) through contact with infected farmed or free-ranging cervids or exposure to contaminated premises. The purpose of this study was to assess the potential for CWD derived from elk to transmit to cattle after intracranial inoculation. Calves (n=14) were inoculated with brain homogenate derived from elk with CWD to determine the potential for transmission and define the clinicopathologic features of disease. Cattle were necropsied if clinical signs occurred or at the termination of experiment (49 months post-inoculation (MPI)). Clinical signs of poor appetite, weight loss, circling, and bruxism occurred in two cattle (14%) at 16 and 17 MPI, respectively. Accumulation of abnormal prion protein (PrP**Sc) in these cattle was confined to the central nervous system with the most prominent immunoreactivity in midbrain, brainstem, and hippocampus with lesser immunoreactivity in the cervical spinal cord. The rate of transmission was lower than in cattle inoculated with CWD derived from mule deer (38%) or white-tailed deer (86%). Additional studies are required to fully assess the potential for cattle to develop CWD through a more natural route of exposure, but a low rate of transmission after intracranial inoculation suggests that risk of transmission through other routes is low. A critical finding here is that if CWD did transmit to exposed cattle, currently used diagnostic techniques would detect and differentiate it from other prion diseases in cattle based on absence of spongiform change, distinct pattern of PrP**Sc deposition, and unique molecular profile.
Last Modified: 08/16/2012
UPDATED CORRESPONDENCE FROM AUTHORS OF THIS STUDY I.E. COLBY, PRUSINER ET AL, ABOUT MY CONCERNS OF THE DISCREPANCY BETWEEN THEIR FIGURES AND MY FIGURES OF THE STUDIES ON CWD TRANSMISSION TO CATTLE ;
CWD to cattle figures CORRECTION
Greetings,
I believe the statement and quote below is incorrect ;
"CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures."
Please see ;
Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease.
" although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). "
shouldn't this be corrected, 86% is NOT a low rate. ...
kindest regards,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Thank you!
Thanks so much for your updates/comments. We intend to publish as rapidly as possible all updates/comments that contribute substantially to the topic under discussion.
re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations
1Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143 2Department of Neurology, University of California, San Francisco, San Francisco, California 94143 Correspondence: stanley@ind.ucsf.edu
Mule deer, white-tailed deer, and elk have been reported to develop CWD. As the only prion disease identified in free-ranging animals, CWD appears to be far more communicable than other forms of prion disease. CWD was first described in 1967 and was reported to be a spongiform encephalopathy in 1978 on the basis of histopathology of the brain. Originally detected in the American West, CWD has spread across much of North America and has been reported also in South Korea. In captive populations, up to 90% of mule deer have been reported to be positive for prions (Williams and Young 1980). The incidence of CWD in cervids living in the wild has been estimated to be as high as 15% (Miller et al. 2000). The development of transgenic (Tg) mice expressing cervid PrP, and thus susceptible to CWD, has enhanced detection of CWD and the estimation of prion titers (Browning et al. 2004; Tamgüney et al. 2006). Shedding of prions in the feces, even in presymptomatic deer, has been identified as a likely source of infection for these grazing animals (Williams and Miller 2002; Tamgüney et al. 2009b). CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures.
snip...
----- Original Message -----
From: David Colby
Sent: Tuesday, March 01, 2011 8:25 AM
Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations
Dear Terry Singeltary,
Thank you for your correspondence regarding the review article Stanley Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner asked that I reply to your message due to his busy schedule. We agree that the transmission of CWD prions to beef livestock would be a troubling development and assessing that risk is important. In our article, we cite a peer-reviewed publication reporting confirmed cases of laboratory transmission based on stringent criteria. The less stringent criteria for transmission described in the abstract you refer to lead to the discrepancy between your numbers and ours and thus the interpretation of the transmission rate. We stand by our assessment of the literature--namely that the transmission rate of CWD to bovines appears relatively low, but we recognize that even a low transmission rate could have important implications for public health and we thank you for bringing attention to this matter.
Warm Regards, David Colby
--
David Colby, PhDAssistant Professor
Department of Chemical Engineering
University of Delaware
====================END...TSS==============
SNIP...SEE FULL TEXT ;
UPDATED DATA ON 2ND CWD STRAIN
Wednesday, September 08, 2010
CWD PRION CONGRESS SEPTEMBER 8-11 2010
Thursday, May 31, 2012
CHRONIC WASTING DISEASE CWD PRION2012 Aerosol, Inhalation transmission, Scrapie, cats, species barrier, burial, and more
CWD has been identified in free-ranging cervids in 15 US states and 2 Canadian provinces and in ≈ 100 captive herds in 15 states and provinces and in South Korea (Figure 1, panel B). SNIP...
Long-term effects of CWD on cervid populations and ecosystems remain unclear as the disease continues to spread and prevalence increases. In captive herds, CWD might persist at high levels and lead to complete herd destruction in the absence of human culling. Epidemiologic modeling suggests the disease could have severe effects on free-ranging deer populations, depending on hunting policies and environmental persistence (8,9). CWD has been associated with large decreases in free-ranging mule deer populations in an area of high CWD prevalence (Boulder, Colorado, USA) (5).
PLEASE STUDY THIS MAP, COMPARE FARMED CWD TO WILD CWD...TSS
PLEASE READ THIS CDC 2012 UPDATE ON CWD RISK FACTORS ;
Saturday, February 18, 2012
Occurrence, Transmission, and Zoonotic Potential of Chronic Wasting Disease
CDC Volume 18, Number 3—March 2012
CWD has been identified in free-ranging cervids in 15 US states and 2 Canadian provinces and in ≈100 captive herds in 15 states and provinces and in South Korea (Figure 1, panel B).
SNIP...
CWD Zoonotic Potential, Species Barriers, and Strains
Current Understanding of the CWD Species Barrier Strong evidence of zoonotic transmission of BSE to humans has led to concerns about zoonotic transmission of CWD (2,3). As noted above, CWD prions are present nearly ubiquitously throughout diseased hosts, including in muscle, fat, various glands and organs, antler velvet, and peripheral and CNS tissue (2,14,15). Thus, the potential for human exposure to CWD by handling and consumption of infectious cervid material is substantial and increases with increased disease prevalence. Interspecies transmission of prion diseases often yields a species-barrier effect, in which transmission is less efficient compared with intraspecies transmission, as shown by lower attack rates and extended incubation periods (3,28). The species barrier effect is associated with minor differences in PrPc sequence and structure between the host and target species (3). Prion strain (discussed below) and route of inoculation also affect the species barrier (3,28). For instance, interspecies transmission by intracerebral inoculation is often possible but oral challenge is completely ineffective (29). Most epidemiologic studies and experimental work have suggested that the potential for CWD transmission to humans is low, and such transmission has not been documented through ongoing surveillance (2,3). In vitro prion replication assays report a relatively low efficiency of CWD PrPSc-directed conversion of human PrPc to PrPSc (30), and transgenic mice overexpressing human PrPc are resistant to CWD infection (31); these findings indicate low zoonotic potential. However, squirrel monkeys are susceptible to CWD by intracerebral and oral inoculation (32). Cynomolgus macaques, which are evolutionarily closer to humans than squirrel monkeys, are resistant to CWD infection (32). Regardless, the finding that a primate is orally susceptible to CWD is of concern. Interspecies transmission of CWD to noncervids has not been observed under natural conditions. CWD infection of carcass scavengers such as raccoons, opossums, and coyotes was not observed in a recent study in Wisconsin (22). In addition, natural transmission of CWD to cattle has not been observed in experimentally controlled natural exposure studies or targeted surveillance (2). However, CWD has been experimentally transmitted to cattle, sheep, goats, mink, ferrets, voles, and mice by intracerebral inoculation (2,29,33). CWD is likely transmitted among mule, white-tailed deer, and elk without a major species barrier (1), and other members of the cervid family, including reindeer, caribou, and other species of deer worldwide, may be vulnerable to CWD infection. Black-tailed deer (a subspecies of mule deer) and European red deer (Cervus elaphus) are susceptible to CWD by natural routes of infection (1,34). Fallow deer (Dama dama) are susceptible to CWD by intracerebral inoculation (35). Continued study of CWD susceptibility in other cervids is of considerable interest.
Reasons for Caution There are several reasons for caution with respect to zoonotic and interspecies CWD transmission. First, there is strong evidence that distinct CWD strains exist (36). Prion strains are distinguished by varied incubation periods, clinical symptoms, PrPSc conformations, and CNS PrPSc depositions (3,32). Strains have been identified in other natural prion diseases, including scrapie, BSE, and CJD (3). Intraspecies and interspecies transmission of prions from CWD-positive deer and elk isolates resulted in identification of >2 strains of CWD in rodent models (36), indicating that CWD strains likely exist in cervids. However, nothing is currently known about natural distribution and prevalence of CWD strains. Currently, host range and pathogenicity vary with prion strain (28,37). Therefore, zoonotic potential of CWD may also vary with CWD strain. In addition, diversity in host (cervid) and target (e.g., human) genotypes further complicates definitive findings of zoonotic and interspecies transmission potentials of CWD. Intraspecies and interspecies passage of the CWD agent may also increase the risk for zoonotic CWD transmission. The CWD prion agent is undergoing serial passage naturally as the disease continues to emerge. In vitro and in vivo intraspecies transmission of the CWD agent yields PrPSc with an increased capacity to convert human PrPc to PrPSc (30). Interspecies prion transmission can alter CWD host range (38) and yield multiple novel prion strains (3,28). The potential for interspecies CWD transmission (by cohabitating mammals) will only increase as the disease spreads and CWD prions continue to be shed into the environment. This environmental passage itself may alter CWD prions or exert selective pressures on CWD strain mixtures by interactions with soil, which are known to vary with prion strain (25), or exposure to environmental or gut degradation. Given that prion disease in humans can be difficult to diagnose and the asymptomatic incubation period can last decades, continued research, epidemiologic surveillance, and caution in handling risky material remain prudent as CWD continues to spread and the opportunity for interspecies transmission increases. Otherwise, similar to what occurred in the United Kingdom after detection of variant CJD and its subsequent link to BSE, years of prevention could be lost if zoonotic transmission of CWD is subsequently identified,
Thursday, February 09, 2012
50 GAME FARMS IN USA INFECTED WITH CHRONIC WASTING DISEASE
SOME HISTORY ON THIS ;
ANOTHER COW GOES DOWN WITH CWD IN LAB STUDIES;
Subject: Re: CWD TO CATTLE by inoculation (ok, is it three or four???)

Date: Wed, 11 Dec 2002 23:20:41 +0000
From: Steve Dealler
Reply-To: Bovine Spongiform Encephalopathy
Organization: Netscape Online member
To: BSE-L
References:
Dear Dr Miller,

I have to admit it was difficult to me to believe either....but in the end I just had to realise that it was true.
When I investigated the age at which cattle actually were becoming infected it was shocking to find that the majority were infected under 1 month of age (and many of them seemed to be within the first week, although the data on this was more shakey, and the rest seemed to be infected in a decreasing slope up to the 7th month.
The question was: just how could the cattle be infected simply so young? What also was turning out was that I could not find any obvious sign of multipoint inoculation and it was as if either there was a major dose arriving at one point or not at all. Again the maths on that was difficult but would probably stand up to the logic. These figures could only be certain in the period on either of the feed ban in the UK in 1988: but then again there was no change in the age distrubution after some other factors are removed since that point.
For a long time we had been wondering why, during the epidemic, the age distribution of cases did not change greatly, when the actual amount of infectivity in the total diet of the battle population may have gone up 10,000fold. Surely, if infection was taking place at many points in an animal's life then they would have been becoming younger when dying of disease as the epidemic progressed?..but this was not seen.
So...when you argue that a lamb is unlikely to have been infected naturally at a single point....I think that this is almost certainly incorrect and that they are indeed infected when exceedingly young and probably at a single point. Also I now believe that the amount of infectivity needed to infect these animals is likely to be very low compared with adults when given orally. (this was all published in the British Food Journal in 2001)

Steve Dealler
"Janice M. Miller" wrote:

> ######## Bovine Spongiform Encephalopathy
#########

>
> I did not mean to imply that it wouldn't be possible for an animal to
> consume that amount of material, especially over a lifetime. I was
> merely pointing out that it is unlikely a lamb would be naturally
> exposed to that amount of material at a single time point early in its
> life and therefore such a short incubation period would not be expected
> to occur under non-experimental conditions.
>
> >>> flounder@WT.NET 12/09/02 12:35PM >>>
>
>
> hello Dr. Miller,
>
> i was curious about this statement;
>
> > It was not a true natural exposure, however, because they fed
>
> > the lambs 2-5 grams of infectious brain, which is very likely a
>
> > much larger dose than would occur under natural conditions.
>
> how do you come to the conclusion that 2-5 grams is a
> 'much larger dose than would occur under natural conditions',
> considering 1/2 to 1 gram is lethal for a cow ?
>
> "FDA has determined that each animal could have consumed, at most and
> in
> total, five-and-one-half grams - approximately a quarter ounce -- of
> prohibited material. These animals weigh approximately 600 pounds."
>
> http://www.fda.gov/bbs/topics/news/2001/new00752.html
>
> if we look at these studies, we will find that
> the 5.5 grams would be more than sufficient to
> infect a cow, if the feed was tainted with TSEs...TSS
>
> please read page 4, 5 and 6 of some 53;
>
> Scientific Steering Committee
> ORAL EXPOSURE OF HUMANS TO THE BSE AGENT:
> INFECTIVE DOSE AND SPECIES BARRIER
>
> http://europa.eu.int/comm/food/fs/sc/ssc/out79_en.pdf
>
> 9 DR. BROWN: If I am not mistaken, and I can be
> 10 corrected, I think a half a gram is enough in a cow, orally;
> 11 in other words, one good dietary-supplement pill.
>
> [FULL TEXT ABOUT 600 PAGES]
> 3681t2.rtf
> http://www.fda.gov/ohrms/dockets/ac/cber01.htm
>
> thank you,
>
> kind regards,
> terry
>
> Janice M. Miller wrote:
> >
> > With scrapie it's believed that most infections occur at or
> shortly
> > after birth, either from exposure to placenta from the lamb's own
> > infected dam or from another placent of another infected ewe that is
> > lambing at the same time. There are several experiments reported,
> > however, in which older sheep from scrapie-free flocks have been put
> in
> > contact with lambing ewes from scrapie flocks and transmission has
> > occurred. In these cases the incubation period appears to be
> longer.
> > Recently we heard in England that they have been able to reproduce
> > scrapie within 6 months (an incredibly short incubation period for
> that
> > disease) by oral exposure of 2-week old lambs. It was not a true
> > natural exposure, however, because they fed the lambs 2-5 grams of
> > infectious brain, which is very likely a much larger dose than would
> > occur under natural conditions. The effect of age on incubation
> period
> > may reflect the amount of lymphoid tissue available in the
> intestinal
> > tract of lambs because they experience a significant amount of
> atrophy
> > in that tissue diromg the first year of life. I don't remember
> anyone
> > suggesting that age plays a role in either the success of
> transmissions
> > or incubation periods when sheep are inoculated initracerebrally.
> That
> > seems to depend mostly on infectious titer of the inoculum and the
> > genetics of the recipient sheep.
> > In CWD no one has found any evidence that placenta is
> infectious
> > so the source of infectivity for transmission is unknown. In the
> highly
> > contaminated wildlife research facility at Colorado they lose over
> 90%
> > of their deer by about 2 years of age so it is likely that those
> animals
> > are infected at a very young age. In the wild, however, they are
> > reporting some positive animals that are much older so while there
> might
> > be some development of resistance with age, it certainly isn't
> complete.
> > I don't know that anyone has reported doing experiments where
> CWD-free
> > deer of different ages were put into a contaminated environment to
> see
> > if the transmission rates or incubation periods would be influenced
> by
> > age.
> >
> >
> >>>>taotm@EARTHLINK.NET 11/26/02 08:24AM >>>
> >>>
> >
> > Dr. Miller,
> >
> > About a year ago there was a report of from a Colorado DoW staffer
> who
> > recalled seeing scrapie sheep in
> > pens near the sickly-looking deer at the Ft. Collins research
> facility.
> > Although there's some debate about
> > whether those sheep actually had scrapie, given the results of the
> > intercerebral tests-- "... The other
> > sheep, necropsied 35 months after inoculation, showed clinical signs
> > and histopathologic lesions that were
> > indistinguishable from scrapie..."-- has there been any attempt to
> > recreate the alleged conditions at Ft.
> > Collins? In other words, an environmental test where scrapie sheep
> > would be put in close proximity to
> > healthy deer? Clearly there's a huge questions about the mechanics
> of
> > jumping the species barrier. But is
> > it possible that this was the way the CWD prion fire was initially
> lit?
> > Farmed sheep to wild cervids?
> >
> > Also, have there been any tests looking at the age at which an
> animal
> > becomes infected? Are younger,
> > smaller animals more at risk? Does the same dose of infectious
> material
> > as given an adult affect them
> > faster or more intensely?
> >
> > thank you,
> >
> > Janet Ginsburg
> >
> > "Terry S. Singeltary Sr." wrote:
> >
> >>hello Janice,
> >>
> >>many thanks for this update.
> >>
> >> > we do not know if the CWD agent in white-tailed deer
> >> > would be equivalent to that obtained from mule deer.
> >>
> >>i was just reading some data where it states;
> >>
> >>Although few white tailed deer were available for biopsy,
> >>findings were consistent with those in mule deer and
> >>support similarity in lymphoid accumulation of PrPCWD
> >>between the species that has been observed post-mortem.
> >>However, because PrPCWD does not appear to accumulate
> >>in lymphoid tissue to the same degree in elk as deer
> >>(T.R. Spraker, unpublished data)
> >>
> >>i am confused?
> >>
> >>thank you,
> >>kind regards,
> >>
> >>terry
> >>
> >>Janice M. Miller wrote:
> >>
> >
> >>> 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 >>>
> >>>>>>
> >>>
> >>>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
=======================================================
-------- Original Message --------
Subject: Re: CWD TO CATTLE by inoculation (ok,is it three or four OR NOW FIVE???)
Date: Mon, 23 Jun 2003 12:36:59 –0500
From: "Janice M. Miller"
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######## Bovine Spongiform Encephalopathy #########
I am happy to provide an update on the experimental inoculation of cattle and sheep with CWD. These are ongoing experiments and updates are normally provided via presentations at meetings. Dr. Hamir has prepared a poster of the following information that will be displayed at 4 upcoming meetings this summer and fall.
Experimental Transmission of Chronic Wasting Disease (CWD) to Cattle and Sheep Progress report - June 23, 2003
Experimental Transmission 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, 4th and 6th years of observation, 7 additional animals have been euthanized due to a variety of health concerns (primarily chronic joint and foot problems). IHC and western blot results indicate that 2 of these animals, necropsied 59 and 63 months after inoculation, were positive for PrPres. One 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. The other PrPres positive animal (#1742) was euthanized after being found in lateral recumbency with a body temperature of 104.6 F. It had not shown prior clinical signs except for some decreased appetite for 2 days. Necropsy revealed only moderate hepatitis and a small renal infarct due to intravascular thrombosis.
Summary of findings on all necropsied animals to date:
Ear tag Date of Survival Disease Clinical Histo- IHC WB no. necropsy period course signs pathology _____________________________________________________________________ 1745 8/18/99 23m 2m + +/- + + 1768 9/22/99 24m 3m + +/- + + 1744 1/29/00 28m 3d +/- - + + 1749 5/20/01 44m NA - - - - 1748 6/27/01 45m NA - - - - 1743 8/21/02 59m NA - - - - 1741 8/22/02 59m NA - - - - 1746 8/27/02 59m 7d +/- +/- + + 1765 11/27/02 62m 1d +/- +/- - - 1742 12/28/02 63m 2d +/- - + + 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 5.75 years of observation we have 5 CWD transmissions to cattle from a group of 13 inoculates. These animals, which were necropsied 23, 24, 28, 59, and 63 months after inoculation, did not show the clinical signs or histopathologic lesions typical of a TSE, but PrPres was detected in brain samples by both immunohistochemistry and western blot. Five other animals necropsied during the 4th, 5th and 6th years of observation have not shown evidence of PrPres and the remaining 3 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. Likely, it would be more difficult to infect cattle by the oral route. Cattle have been inoculated orally at the University of Wyoming with the same inoculum used in this experiment, and 5.75 years into the study the animals remain healthy (personal communication, Dr. Beth Williams).
Experimental Transmission of CWD 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 47 months after inoculation.
Summary: After 4 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.
-------- Original Message --------
Subject: Re: CWD TO CATTLE by inoculation (ok, is it three or four OR NOW FIVE???)
Date: Mon, 23 Jun 2003 09:25:27 –0500
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
######## Bovine Spongiform Encephalopathy #########
Greetings List Members,
i hear now that a 5th cow has gone done with CWD from the studies of Amir Hamir et al. will Dr. Miller please confirm or deny this please, and possibly explain why this has not made the news, if in fact this is the case?
seems these cows infected with CWD/TSE did not display the usual BSE symptoms. i wonder how many more are out there in the field? course, we will never know unless someone starts rapid TSE/BSE testing in sufficient numbers to find...
thank you, kind regards, terry
Date: Sat, 23 Nov 2002 18:54:49 -0600 Reply-To: BSE Sender: BSE From: "Terry S. Singeltary Sr." Subject: CWD TO CATTLE by inoculation (ok, is it three or four???)
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.
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.
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
Saturday, June 09, 2012
USDA Establishes a Herd Certification Program for Chronic Wasting Disease in the United States
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
Interspecies transmission studies afford the opportunity to better understand the potential host range and origins of prion diseases. The purpose of these experiments was to determine susceptibility of white-tailed deer (WTD) to scrapie and to compare the resultant clinical signs, lesions, and molecular profiles of PrPSc to those of chronic wasting disease (CWD). We inoculated WTD intracranially (IC; n = 5) and by a natural route of exposure (concurrent oral and intranasal (IN); n = 5) with a US scrapie isolate.
All deer were inoculated with a 10% (wt/vol) brain homogenate from sheep with scrapie (1ml IC, 1 ml IN, 30 ml oral). All deer inoculated by the intracranial route had evidence of PrPSc accumulation. PrPSc was detected in lymphoid tissues as early as 7 months-post-inoculation (PI) and a single deer that was necropsied at 15.6 months had widespread distribution of PrPSc highlighting that PrPSc is widely distributed in the CNS and lymphoid tissues prior to the onset of clinical signs. IC inoculated deer necropsied after 20 months PI (3/5) had clinical signs, spongiform encephalopathy, and widespread distribution of PrPSc in neural and lymphoid tissues.
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.
PO-041: Susceptibility of domestic cats to CWD infection
Amy Nalls, Jeanette Hayes-Klug, Kelly Anderson, Davis Seelig, Kevin Carnes, Susan Kraft, Edward Hoover, Candace Mathiason
Colorado State University; Fort Collins, CO USA
Domestic and non-domestic cats have been shown to be susceptible to feline spongiform encephalopathy (FSE); very likely due to consumption of bovine spongiform encephalopathy (BSE) contaminated meat. Because domestic and free-ranging nondomestic felids scavenge cervid carcasses, including those in areas affected by chronic wasting disease (CWD), we evaluated the susceptibility of domestic cats to CWD infection experimentally. Groups of n = 5 cats each were inoculated either intracerebrally (IC) or orally (PO) with CWD-infected deer brain homogenate.
Between 40 and 43 months two IC-inoculated cats developed slowly progressive symptoms including weight loss, anorexia, polydipsia, patterned motor behaviors, and ataxia”’ultimately mandating euthanasia. PrPCWD was detected in the brains of these animals by western blot, immunohistochemistry (IHC), and quaking-induced conversion (RT-QuIC) assays. No clinical signs of TSE were detected in the remaining primary passage cats at 86 months pi. Feline-adapted CWD (FelCWD) was sub-passaged into groups (n = 4 or 5) of cats by IC, PO, and IP/SQ routes.
All 5 IC inoculated cats developed symptoms of disease 20–24 months pi (approximately half the incubation period of primary passage). Additional symptoms in these animals included increasing aggressiveness and hyper responsiveness. FelCWD was demonstrated in the brains of all the affected cats by western blot and IHC. Currently, 3 of 4 IP/SQ, and 1 of 4 PO inoculated cats have developed abnormal behavior patterns consistent with the early stage of feline CWD. Magnetic resonance imaging (MRI) has been performed on 11 cats (6 clinically ill, 2 asymptomatic, and 3 age-matched negative controls). Abnormalities were detected in 4 of 6 clinically ill cats and included multifocal signal changes consistent with inflammation, ventricular size increases, more prominent sulci, and white matter tract cavitation.
These results demonstrate that CWD can be transmitted and adapted to the domestic cat, and raise the potential for cervid-to-feline transmission in nature.
SEE ;
Thursday, May 31, 2012
CHRONIC WASTING DISEASE CWD PRION2012 Aerosol, Inhalation transmission, Scrapie, cats, species barrier, burial, and more

posted by Terry S. Singeltary Sr. at 12:28 PM

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