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Friday, August 07, 2015

Texas CWD Captive, and then there were 4 ?

Texas CWD Captive, and then there were 4 ?

 

Rancher: 4 deer from Medina County test positive for CWD

 

Chronic wasting disease outbreak being monitored by Texas Animal Health Comm­ission, Texas Parks and Wildlife Department

 

Updated TODAY, 2:58 PM

 

By Pilar Arias

 

Reporter

 

SAN ANTONIO - Texas Mountain Ranch owner Robert Patterson says four deer from his facility in Medina County have tested positive for chronic wasting disease.

 

 Patterson has been working with the Texas Animal Health Commission and Texas Parks and Wildlife Department since one of his captive white-tailed deer tested positive for CWD in June.

 

snip...

 

He said 42 deer have been killed and tested since July 28, and three additional positives were the result. He added that all four deer confirmed to have the disease were males from the same father, which leads him to believe the problem is genetic.

 

snip...

 


 

why in the world was there not already a CWD EMERGENCY RESPONSE PLAN FOR CAPTIVES already set up and ready to go in Texas ?

 

what’s the cwd task force been doing?

 

what happened behind closed door sessions?

 

why is it taking so long for the TAHC et al to report these results ? (can it be we are waiting to find someone that can find a false negative, maybe like the mad cow in Texas that was covered up for 7 months so the BSE MRR policy could be validated first? I’m just guessing out loud) of the fact that Texas waited 10 years to finally test for CWD, right where I told them a decade earlier where it would be. for 10 years that cwd walked or was trucked across Texas. or longer.

 

when is the testing on the rest of the herd be done?

 

what about cohorts of cwd positives, their trace outs, those herds?

 

why aren’t those herds quarantined yet ?

 

where are the reports?

 

what’s the rush, right $$$

 

let’s see just how much, and how far we can spread this CWD TSE prion.

 

this is absolutely crazy.

 

 Thursday, August 06, 2015

 

WE HAVE LOST TEXAS TO CWD TASK FORCE CATERING TO INDUSTRY

 


 

Friday, August 7, 2015

 

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

 


 

PrPSc detection and infectivity in semen from scrapie-infected sheep

 

Richard Rubenstein,1 Marie S. Bulgin,2 Binggong Chang,1 Sharon Sorensen-Melson,2 Robert B. Petersen3 and Giuseppe LaFauci4 Correspondence Richard Rubenstein richard.rubenstein@downstate. edu Received 13 October 2011 Accepted 3 February 2012 1Departments of Neurology and Physiology/Pharmacology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA 2University of Idaho, Caine Veterinary Teaching and Research Center, 1020 E. Homedale Road, Caldwell, ID 83607, USA 3Departments of Pathology Neuroscience, and Neurology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44120, USA 4New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA

 

A scrapie-positive ewe was found in a flock that had been scrapie-free for 13 years, but housed adjacent to scrapie-positive animals, separated by a wire fence. Live animal testing of the entire flock of 24 animals revealed seven more subclinical scrapie-positive ewes. We hypothesized that they may have contracted the disease from scrapie-positive rams used for breeding 4 months prior, possibly through the semen. The genotypes of the ewe flock were highly scrapiesusceptible and the rams were infected with the ‘Caine’ scrapie strain having a short incubation time of 4.3–14.6 months in sheep with 136/171 VQ/VQ and AQ/VQ genotypes. PrPSc accumulates in a variety of tissues in addition to the central nervous system. Although transmission of prion diseases, or transmissible spongiform encephalopathies, has been achieved via peripheral organ or tissue homogenates as well as by blood transfusion, neither infectivity nor PrPSc have been found in semen from scrapie-infected animals. Using serial protein misfolding cyclic amplification followed by a surround optical fibre immunoassay, we demonstrate that semen from rams infected with a short-incubation-time scrapie strain contains prion disease-associatedseeding activity that generated PrPSc in sPMCA (serial protein misfolding cyclic amplification). Injection of the ovinized transgenic mouse line TgSShpPrP with semen from scrapie-infected sheep resulted in PrPSc-seeding activity in clinical and, probably as a result of the low titre, nonclinical mouse brain. These results suggest that the transmissible agent, or at least the seeding activity, for sheep scrapie is present in semen. This may be a strain-specific phenomenon.

 

RESULTS

 

The use of SOFIA alone to detect PrPSc in semen samples from scrapie-infected sheep was unsuccessful (data not shown). In previous studies (Rubenstein et al., 2010, 2011), we also reported that SOFIA alone was unable to detect PrPSc in blood and urine from scrapie-infected sheep and cervids with chronic wasting disease. However, in combination with sPMCA, which utilizes PASA, PrPSc in blood and urine was detectable. The level of PrPSc detected was dependent on the number of serial cycles of PMCA. Furthermore, amplification is efficient independent of the genotypes of the PrPC and PrPSc (Rubenstein et al., 2010, 2011). The level of PrPSc measured by SOFIA following sPMCA80 and sPMCA120 (Fig. 1) was similar to that found in urine (Rubenstein et al., 2011) and significantly less than that found in blood (Rubenstein et al., 2010) from scrapieinfected sheep. This suggests that the PASA found in the semen of these animals is similar to that for urine from infected animals, approximately 1 attogram ml21. However, it is not possible to determine whether prion-seeding activity is actually PrPSc (Rubenstein et al., 2011).

 

The ovinized PrP transgenic mouse line, TgSShpPrP, was analysed for ovine PrPC expression. Serial twofold dilutions of brain homogenates from TgSShpPrP mice and wild-type (WT) mice on the same FVB genetic background were analysed by Western blotting. PrPC was immunostained using the PrP-specific mAb, 08-6/2F7-2F11. The dilutions producing equivalent PrPC immunostaining between the two mouse lines indicate that the level of expression of sheep PrPC in the brains of TgSShpPrP mice is approximately fourfold greater than mouse PrPC in the WT mice (Fig. 2).

 

The ability of TgSShpPrP mice to support replication of the sheep prion agent was analysed and is summarized in Table 2. Brain homogenate from scrapie-infected ram #8001, which was positive for PK-resistant PrPSc by Western blotting (Fig. 3a, lanes 3–4), was used to infect TgSShpPrP mice. Injection of nine TgSShpPrP mice by the intracerebral (IC) route with a 10% brain homogenate from ram #8001 had a mean incubation period of 167±7 days, indicating that these mice support replication of the ovine prion agent. Western blotting of brain from clinical TgSShpPrP mice demonstrated the presence of PK-resistant PrPSc (Fig. 3a, lane 8). In contrast, TgSShpPrP mice showed no clinical signs or PrPSc after over 520 days following IC injection of either a 10% normal sheep brain (NSB) homogenate or a 10% ME7 mouse-adapted scrapie strain brain homogenate (Table 2).

 

Semen samples from scrapie-positive rams (# 3272, 7031, 7035 and 8001) were injected IC into TgSShpPrP mice (five mice per semen sample) to bioassay for prion infectivity (Table 2). One TgSShpPrP mouse from the ram #7031 semen sample group and one from the ram #3272 semeninjected group showed clinical signs after an incubation period of 310 and 655 days, respectively. Western blotting of the brain from these mice demonstrated PK-resistant PrPSc (Fig. 3a and b). Interestingly, the mouse from the ram #3272 group did not display any clinical signs at 648 days post-injection (p.i.), but by 655 days p.i. the animal was at the end stage of clinical disease. This is about half the time it typically takes mice to proceed through the same clinical disease course. The remaining mice from these groups, as well as all the mice from the other ram semen-injected groups did not display any clinical disease throughout the entire experiment (.670 days p.i.).

 

Animals were randomly selected from the groups of nonclinical TgSShpPrP mice injected with semen samples from ram #3272 (385 days p.i.), 7031 (385 days p.i.), 7035 (350 days p.i.) and 8001 (335 days p.i.). TgSShpPrP mouse brain homogenates were prepared and analysed by Western blotting for the presence of PrPSc. PK-resistant PrPSc, indicative of prion disease, was detected in the brain homogenates of all the semen-injected non-clinical TgSShpPrP mice (Fig. 3b, lane 2; Fig. 4 lanes 6, 8, 10 and 12). Interestingly, all of the PK-resistant PrPSc profiles from the non-clinical mice injected with different semen samples were similar with a prominent protein band at 27–30 kDa, representing the truncated diglycosylated PrP, a less intense immunostained band at 23–25 kDa indicative of the truncated monoglycosylated form of PrP and a lighter, truncated unglycosylated PrP form at 19–20 kDa. Additional analysis of random, non-clinical TgSShpPrP mice selected from the semen-injected groups at 523 days p.i. produced similar positive Western blot results and the same PrPSc profile (data not shown). In contrast, and as expected, clinical TgSShpPrP mice injected with either ram #8001 brain homogenate (Fig. 3a, lane 8; Fig. 4, lane 2), or semen from ram #7031 (Fig. 3a, lane 10) and 3272 (Fig. 3b, lane 6) had a PK-resistant PrPSc pattern consisting of three intensely immunostained bands. A similar pattern of three intensely immunostained bands was also seen in a nonclinical mouse from ram #3272 semen-injected group at 648 days p.i. (Fig. 3b, lane 4), just 7 days before another mouse from this group displayed extensive clinical disease. None of the five TgSShpPrP mice/group injected IC with semen from the uninfected rams displayed any clinical signs or PK-resistant PrPSc by 650 days p.i. (data not shown). The IHCs performed on all reproductive tissues (prostrate, epididymis, vesicular glands and testes) of the above rams were negative for PrPSc (Table S2). Ram #8031 (ARQ/ ARQ) also tested negative by IHC on RAMALT and third eyelid and his brain and all other tissues tested were IHC negative for PrPSc when euthanized following semen collection (Table S2). Western blot analysis of brain tissue from ram #8031 was negative for PK-resistant PrPSc. Western blotting of the samples following 40 cycles of serial PMCA (sPMCA40) using ram #8031 brain tissue as a seed was also negative for PK-resistant PrPSc (data not shown) presumably due to the limitations of assay sensitivity. However, using sPMCA40, PASA in ram #8031 brain tissue could be detected and the product (i.e. PrPSc) measured by SOFIA with signal intensities (sample/background) of 39.8±2.1 compared with 1.01±0.02 for uninfected control sheep brain.

 

DISCUSSION

 

The decision to use rams from the scrapie-positive flock to breed ewes in the sentinel flock resulted from the scarcity and difficulty of finding 136V/V and A/V rams in private certified scrapie-free flocks and the prevalent belief at that time that rams do not transmit scrapie as indicated by the National Scrapie Surveillance Plan (2010). Current USDA Scrapie Eradication Uniform Methods and Rules (2005) do not require the quarantining of flocks following the introduction of exposed rams. Furthermore, the European Food Safety Authority recently reached the same conclusion that the risk of TSE transmission associated with semen and embryos collected from classical scrapie incubating sheep and goats ranges from negligible to low [EFSA Panel on Biological Hazards (BIOHAZ), 2010].

 

Despite extensive research, the natural routes of TSE transmission are still rather poorly understood. Alimentary excretion and oral ingestion contributes to horizontal transmission, but long incubation periods make it difficult to link clinical cases to the original source of infection. Host genetic factors, especially in sheep scrapie, make epidemiological interpretations even more difficult, and the existence of different TSE strains brings further complexity. Understanding the risks of transmission, especially those posed by reproductive technologies, requires information on the presence and levels of infectivity in various body tissues, which typically entails detection of PrPSc by immunohistochemical or immunoblotting assays. However, since the ability to detect PrPSc does not necessarily equate with the amount of infectivity, bioassays in mice are also required.

 

The general conclusion from research to date is that the risk of TSE infection by semen from sheep, goats and cattle is extremely low. Cross-contamination of the semen samples used in this study is one explanation for the infectivity detected in the semen samples from the infected animals. However, TgSShpPrP mice injected with semen from the uninfected rams did not show any sign of disease or the presence of PrPSc in their brains. The results of the current study demonstrate detection of PASA in semen as well as the presence of PrPSc in transgenic mice following IC injection. The detection of PASA was performed by using normal brain homogenate as a PrPC source from sheep with a genotype that, in some cases, did not match the genotype of the ram semen samples. It is doubtful that this had any negative influence on PASA amplification of the semen samples since previous studies using mismatched genotypes similar to that for semen did not hinder amplification in blood and urine (Rubenstein et al., 2011, 2011). The detection of the infectious agent in semen by bioassays in ovinized transgenic mice contrasts with the previous report by Sarradin et al. (2008). Sarradin et al. (2008) examined the role of semen in sheep scrapie transmission by analysing whether semen (i.e. seminal plasma and spermatozoa) could infect and cause disease in the tg338 transgenic mouse line, which overexpresses the permissive V136R154Q171 allele of the ovine prion protein. None of the tg338 mice injected with semen from the VRQ/VRQ genotype or from the ARR/ARR control ram showed any clinical signs during the period of the experiment. The semen samples differed between the two studies, as did the transgenic mouse lines, and most likely the scrapie strain. While both the VRQ and ARQ genotypes are more sensitive to scrapie infection than the ARR genotype, it is conceivable that in the transgenic mouse bioassay the ARQ protein confers greater susceptibility to semen-derived PrPSc. PrP in sperm is known to undergo different processing than that in brain (Shaked et al., 1999; Ecroyd et al., 2005). Further, the impact of alanine substitutions can be substantial since the threonine to alanine mutation at position 183 of the human prion protein is linked to a familial disease and results in retention of the prion protein in the endoplasmic reticulum due to structural changes in the protein (Capellari et al., 2000). Whether or not these factors were responsible for the differences in the final outcomes of these studies remains to be determined. However, it seems premature to rule out the potential of semen-associated-seeding activity as a factor in the transmission of scrapie.

 

Ram #8031 is of particular interest. He was euthanized due to an overabundance of ARQ/ARQ and showed no clinical signs at the time of death at age 16 months. All postmortem tissues were IHC negative (Table S2) and yet sPMCA80 and sPMCA120 followed by SOFIA showed that PASA was present in the semen of this ram. No doubt this ram was infected and subclinical. He had been born and raised in a highly contaminated environment, but possessed a long incubation time genotype. Typical of this strain, he would not have shown clinical signs or positive testing utilizing IHC for 3–5 years. This supports and strengthens our view that the assay used in this study is more sensitive than the presently accepted IHC for early detection of scrapie and could be of value as a live animal test.

 

We tend to believe that a positive ram was the likely source of the scrapie-infected ewes, if not from semen, then by another type of contact. All but one of the affected ewes were VRQ/VRQ; the incubation time of the ‘Caine’ strain of scrapie normally in these genotypes is 4–7 months (Bulgin et al., 2006; Hamir et al., 2009), suggesting that the exposure occurred during the period when the rams were placed with the ewes for breeding. However, the presence of the infectious agent in the semen of the 136AV and VV rams infected with the ‘Caine’ strain of scrapie, adds another intriguing possibility.

 

An interesting question is why it took so long for the disease to present itself when the first exposure of the flock during breeding to positive rams occurred 4 years previously. During the preceding 7 years, even though the flock was genetically susceptible, there was no scrapie transmission. The disease onslaught definitely appears to be promoted by the change in genetic composition of the sentinel flock and their degree of susceptibility. When the 136VV and AV rams were first introduced to the flock in 2004, the ewes were all 136AA. Thus, the population slowly shifted to become more susceptible as the 136V genotype was selected for. It is noteworthy that every one of the 136VV ewes in the flock (26 %) was affected. Only one 136AV ewe was affected in spite of the fact that AV ewes made up the majority of the flock (57.9 %). Interestingly, of the VV ewes, two had been in the flock for 3 years, two for 2 years and three were yearlings.

 

In summary, it seems premature to rule out the potential of semen-associated-seeding activity as a factor in transmission of scrapie. In that regard, experiments are currently under way to assess the transmissibility of the PrPSc from the clinically normal mice that had been infected with sheep semen as well as the material produced by PMCA using a semen seed. These results will demonstrate whether the seeding activity found in semen is competent to promote scrapie transmission. Also, demonstration of natural transmission of scrapie in sheep by semen will have to be confirmed by inoculation of highly susceptible oestrous ewes via artificial insemination using semen collected from positive ‘Caine’ strain scrapie-infected rams since this may be a strain-specific phenomenon.

 


 

 PrPSc has been detected in sheep, deer, and hamster blood, both at terminal stages of disease and in pre-symptomatic animals [21], [36], [45]–[48] and in CSF and urine from naturally and experimentally infected animals [22], [34], [48]–[50]. Furthermore, epidemiologic studies have demonstrated the presence of prion infectivity in blood and plasma from vCJD cases [51]–[54]. It is possible that the level of infectivity and/or PrPSc is too low to be detected or that there may be various forms of sCJD with subtle differences, which reflects varied amounts of infectivity in the blood. We have shown that PrPSc is detectable by western blotting of samples from CNS and lymphoid tissues, including tonsil, of both vCJD and sCJD patients. We also demonstrated that PrPSc is detectable by SOFIA in unconcentrated, and even highly diluted, CNS and non-CNS tissues from human prion disease samples, as well as in CSF from sCJD patients. Thus, our assay could be used for antemortem diagnosis of both sCJD and vCJD. In addition, our data suggests that PMCA of blood followed by SOFIA should be pursued as a non-invasive assay for antemortem diagnosis of vCJD. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066352

 

Sunday, August 02, 2015

 

TEXAS CWD, Have you been ThunderStruck, deer semen, straw bred bucks, super ovulation, and the potential TSE Prion connection, what if?

 


 

 

Saturday, August 01, 2015

 

Texas CWD Medina Captive Two more deer test positive for chronic wasting disease CWD TSE Prion

 


 

Sunday, August 02, 2015

 

TEXAS CWD, Have you been ThunderStruck, deer semen, straw bred bucks, super ovulation, and the potential TSE Prion connection, what if?

 


 

Sunday, July 26, 2015

 

TEXAS IN MELT DOWN MODE OVER CAPTIVE CWD AND THEY ARE PUTTING LIPSTICK ON THAT PIG AND TAKING HER TO THE DANCE LIKE MAD COW DISEASE

 


 

Thursday, July 23, 2015

 

Chronic Wasting Disease (CWD) 101 Drs. Walter Cook & Donald S. Davis

 


 

Tuesday, July 28, 2015

 

TEXAS Kills 35 Deer at Medina County Ranch (Texas Captive CWD)

 


 

Tuesday, July 21, 2015

 

*** Texas CWD Medina County Herd Investigation Update July 16, 2015 ***

 


 

Friday, July 17, 2015

 

TPW Commission Holds Special Meeting on Chronic Wasting Disease

 


 

Wednesday, July 01, 2015

 

TEXAS Chronic Wasting Disease Detected in Medina County Captive Deer

 


 

Thursday, July 09, 2015

 

TEXAS Chronic Wasting Disease (CWD) Herd Plan for Trace-Forward Exposed Herd with Testing of Exposed Animals

 


 

Tuesday, July 14, 2015

 

Texas Parks and Wildlife Commission Special Meeting Thursday on Chronic Wasting Disease CWD

 


 

Rare report of deer disease in Texas causes stir

 

Houston Chronicle

 

Rare report of deer disease in Texas causes stir, especially since it’s the 8 case of CWD documented in Texas, and the first case of CWD in Captive deer.

 

here is how I would have titled this article, and why.

 

Shannon Tompkins Finally Breaks Silence on Texas First Captive CWD Case and Starts Off Spreading False Information About Risk Factors. ...

 

Thursday, July 16, 2015

 


 

Wednesday, March 18, 2015

 

Chronic Wasting Disease CWD Confirmed Texas Trans Pecos March 18, 2015

 


 

Wednesday, March 25, 2015

 

Chronic Wasting Disease CWD Cases Confirmed In New Mexico 2013 and 2014 UPDATE 2015

 


 

Thursday, May 02, 2013

 

*** Chronic Wasting Disease (CWD) Texas Important Update on OBEX ONLY TEXTING

 


 

Monday, February 11, 2013

 

TEXAS CHRONIC WASTING DISEASE CWD Four New Positives Found in Trans Pecos

 


 

Tuesday, July 10, 2012

 

Chronic Wasting Disease Detected in Far West Texas

 


 

Monday, March 26, 2012

 

Texas Prepares for Chronic Wasting Disease CWD Possibility in Far West Texas

 


 

***for anyone interested, here is some history of CWD along the Texas, New Mexico border, and my attempt to keep up with it...terry

 

snip...

 

see history CWD Texas, New Mexico Border ;

 

Monday, March 26, 2012

 

3 CASES OF CWD FOUND NEW MEXICO MULE DEER SEVERAL MILES FROM TEXAS BORDER

 


 

Sunday, October 04, 2009

 

CWD NEW MEXICO SPREADING SOUTH TO TEXAS 2009 2009 Summary of Chronic Wasting Disease in New Mexico New Mexico Department of Game and Fish

 


 

Wednesday, August 05, 2015

 

*** Ohio confirms to me Chronic Wasting Disease CWD Spreads 19 confirmed cases to date ***

 

Just got off the phone with Christy Clevenger of Ohio

 

Ohio Department of Agriculture March 2012 – Present (3 years 6 months)Reynoldsburg, Ohio CWD program

 

Ms. Clevenger confirmed, to date, from the Yoder debacle, 1 confirmed case of CWD from the Hunting Preserve, 2 confirmed cases from the Breeding Farm, and 16 confirmed cases of CWD from the Breeder Depopulation, with a total to date of 19 cases of CWD in Ohio...

 

Terry

 


 

Thursday, August 06, 2015

 

Michigan DNR confirms third deer positive for CWD; hunter participation is critical this fall

 


 


 

Tuesday, August 4, 2015

 

FDA U.S. Measures to Protect Against BSE

 


 

 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

 

Terry S. Singeltary, Sr Bacliff, Tex

 

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.

 


 

 

TSS

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