RT-QuIC amplification of CWD prions in winter ticks (Dermacentor albipictus) collected from North American elk (Cervus canadensis) in a CWD-endemic area
Abstract
Chronic wasting disease (CWD) is a progressive and fatal spongiform encephalopathy of deer and elk species, caused by a misfolded variant of the normal prion protein. Horizontal transmission of the misfolded CWD prion between animals is thought to occur through shedding in saliva and other forms of excreta. The role of blood in CWD transmission is less clear, though infectivity has been demonstrated in various blood fractions. Blood-feeding insects, including ticks, are known vectors for a range of bacterial and viral infections in animals and humans, though to date there has been no evidence for their involvement in prion disease transmission. In the present study, we evaluated winter ticks ( Dermacentor albipictus ) collected from 136 North American elk ( Cervus canadensis ) in a CWD-endemic area for evidence of CWD prion amplification using the real time quaking-induced conversion assay (RT-QuIC). Although 30 elk were found to be CWD-positive (22%) postmortem, amplifiable prions were found in just a single tick collected from an elk in advanced stages of CWD infection, with some evidence for prions in ticks collected from elk in mid-stage infection. These findings suggest that further investigation of ticks as reservoirs for prion disease may be warranted.
Importance
This study reports the first finding of detectable levels of prions linked to chronic wasting disease in a tick collected from a clinically infected elk. Using the real time quaking-induced conversion assay (RT-QuIC), evidence of amplifiable CWD prions was also found in ticks collected from elk in earlier stages of disease. Observed levels were at the lower end of our detection limits, though our findings suggest that additional research evaluating ticks collected from animals in late-stage disease may be warranted to further evaluate the role of ticks as potential vectors of chronic wasting disease. 233 In summary, we report that RT-QuIC may serve as a useful tool for evaluating the role of ticks and other insects as reservoirs of PrPCWD. Amplifiable levels of PrPCWD 234 in the present 235 study were low, and likely limited to ticks collected from animals in later stages of disease. 236 Additional studies focusing on insect vectors feeding on terminally infected cervids and the 237 biological relevance of any detectable CWD prions in these vectors are warranted to more fully 238 characterize the role of external parasites in prion transmission.
SATURDAY, DECEMBER 21, 2013
Parelaphostrongylus (Brainworm) Infection in Deer and Elk and the potential for CWD TSE prion consumption and spreading there from ?
Greetings everyone et al, and Merry Christmas,
I am hoping, and praying, that 2014 will bring forth much needed funding for the TSE prion scientist around the globe.
I brought up a concern for a worm long ago, that gets in the brains of cervids, and then the worm gets excreted via feces, and then deer forage and eat that worm. if the host cervid of this worm has CWD, could this later transmit CWD?
I was concerned about this long ago, still am. I was curious what any else might think about this potential mode of transmission with cwd ?
there is much cwd risk factor now with soil, and now the potential exists via plants, so I was just pondering out loud here, is it possible that some cwd is being spread, by the Parelaphostrongylus (Brainworm), after sucking up on a CWD infected cervids brain, and then being discarding via feces by that same CWD infected cervid, soaking up the prions via the feces, laying in wait, for a CWD free cervid to come scoop up and eat that Parelaphostrongylus (Brainworm), that has been extremely exposed to the TSE prion ?
CONFIDENTIAL
SEAC 97/2
Annex 2
UNITED KINGDOM ACCREDITATION SERVICE (UKAS)
ASSESSMENT REPORT
Other organisms
Transmission of TSEs through ectoparasites has been postulated by Lupi5. Post et al6 fed larvae of meat eating and myiasis causing flies with brain material from scrapie infected hamsters. Two days after eating infected material, the larvae showed high amounts of PrPSc by Western blot. In further studies, the inner organs of larvae, which had been fed with scrapie brain, were extracted and fed to hamsters. Six out of eight hamsters developed scrapie. Two out of four hamsters fed on scrapie infected pupae subsequently developed scrapie.
http://www.seac.gov.uk/papers/97-2.pdf
SEAC 97/2 Annex 3
Published research and Previous SEAC and European Commission DG
Health and Consumer Protection Scientific Steering Committee (SSC)
advice
Sewage sludge
In a June 1996 statement1 , along with recommendations for handling waste material from cattle, SEAC considered the practice of spreading of sewage sludge on land in the context of the risk of Specified Risk Material (SRM) particles from abattoir waste potentially entering the sewerage system. Provided the particulate matter was retained and disposed of as SRM, the committee was content for abattoirs to discharge their liquid waste to sewers and for sewage sludge to be disposed of by spreading on land. Any small particulate matter passing through the trap would be diluted to such an extent as to pose negligible risk.
Gale and Stanfield2 estimated the risks from sewage sludge based on the assumption that 1% of brain and spinal cord is lost to the sewer from abattoirs. The model predicts a risk of BSE transmission of 71 x 10-5 cow-1 year–1 for cattle grazing on land to which sewage sludge has been applied. The authors conclude that the dose consumed by grazing cattle is insufficient to sustain the BSE epidemic in the UK cattle herd. The risk from sewage sludge derived from human, cattle and other species remains theoretical.
Birds
The possibility that birds may act as possible transmitters of BSE was considered by the SSC opinion 7-8 November 20023 (provided) “Necrophagous birds as possible transmitters of TSE/BSE”. The SSC concluded that birds could have theoretically ingested infectious material through fallen stock. It had been proposed that the spread of the ingested infectious material could occur through faecal contamination, as it is unlikely the pathological prion protein would be destroyed in the digestive tract. The SSC concluded that the possibility of active replication of PrPSc in birds is remote but agreed that such pathways of transmission cannot be excluded given these birds cover great distances during migration.
Rodents
Concepcion and Padlan4 have postulated that inadvertent ingestion of infected rodent parts, possibly droppings, may be a potential mode of transmission of TSEs. This postulate is based on sequence homology comparisons, which showed a close similarity between sequences of human and rodent prion proteins in a peptic fragment
1 http://www.seac.gov.uk/statements/state07jun96.htm
2 Gale P. and Stanfield G. (2001) Towards a quantitative risk assessment for BSE in sewage sludge J. Appl. Microbiol. 91, 563-569
3 http://ec.europa.eu/food/fs/sc/ssc/out295_en.pdf
4 Concepcion G.P. and Padlan E.A. (2003) Are humans getting ‘mad cow disease’ from eating beef or something else? Med. Hypotheses 60, 699-701 (that could result from gastric digestion) that corresponds to a PrP fragment that is protease resistant and infective. This remains a postulate.
Other organisms
Transmission of TSEs through ectoparasites has been postulated by Lupi5 . Post et al6 fed larvae of meat eating and myiasis causing flies with brain material from scrapieinfected hamsters. Two days after eating infected material, the larvae showed high amounts of PrPSc by Western blot. In further studies, the inner organs of larvae, which had been fed with scrapie brain, were extracted and fed to hamsters. Six out of eight hamsters developed scrapie. Two out of four hamsters fed on scrapie infected pupae subsequently developed scrapie.
At SEAC36 (September 1996) members considered a paper by Wisniewski et al7 , (data also published subsequently in a paper by Rubenstein et al8 ) who inoculated suspensions of mites from five Icelandic scrapie affected farms into mice, intracerebrally and intraperitoneally. Of 71 mice inoculated, 10 developed clinical TSE, with detection of PrPSc in their brains by Western blot. PrPSc was demonstrated in mite concentrates from one of the farms. The committee also received a presentation on a survey of the prevalence of mites in various cereal products. Some mites were of the same species in the Wisniewski study. SEAC concluded that it was essential that the work on mites be repeated to validate the conclusions. SEAC did not consider that the conclusions raised any public health concerns on mites and TSEs.
Post et al6 found that mites exposed to hamster scrapie and subsequently fed to hamsters did not cause clinical scrapie in the hamsters. Defra has funded two projects to study transmission of TSEs from hay mites, which are now completed.
Project SE1829
Mites of 3 different species that are present on farms in the UK were fed on material contaminated with BSE infected cow brain. The mites were found not to carry sufficient amounts of infection to cause TSE in mouse bioassays. Similarly when the exposed mites were cultured for 2-3 generations no TSE transmission was detectable by mouse bioassay. Attempts to detect conserved DNA sequences from mammalian PrP genes in mite DNA extracts were unsuccessful indicating that mites do not have PrP-like proteins. The results suggest that mites are unlikely to be significant vectors or reservoirs of TSE diseases.
5 Lupi O. (2005) Risk analysis of ectoparasites acting as vectors for chronic wasting disease. Med. Hypotheses 65, 47-54
6 Post K. (1999) Fly larvae and pupae as vectors for scrapie. Lancet 354, 1969-1970
7 Wisniewski H.M., Sigurdarson S., Rubenstein R., Kascsak R.J, Carp R.I. (1996) Mites as vectors for scrapie. Lancet 347, 1114
8 Rubenstein R., Kascsak R.J., Carp, R.I., Papini M., LaFauci G., Sigurarson S., and Wisniewski HM (1998) Potential role of mites as a vector and/or reservoir for scrapie transmission. Alzheimer’s Disease Review 3, 52-56
Project SE1828
Fifteen sheep farms with high incidence scrapie and fifteen farms with low (no reported) incidence scrapie were examined for mite infestation. Overall the results (mite fauna) were closely similar and no clear differences between high and low incidence farms were identified. Samples of mites were cultured to test their ability to carry TSEs. Mice challenged with the mite samples failed to reveal any evidence of infectivity.
Search terms with atypical scrapie on Pubmed:
The following search criteria were used with no result Environmental transmission of atypical scrapie
Atypical scrapie and environment
Atypical scrapie and mites
Atypical scrapie and foxes
Atypical scrapie and birds
Transmission of atypical scrapie by rodents: this revealed use of rodent models rather than transmission by mice in the field.
snip...see;
kind regards, terry
SATURDAY, DECEMBER 21, 2013
Parelaphostrongylus (Brainworm) Infection in Deer and Elk and the potential for CWD TSE prion consumption and spreading there from ?
Successful transmission of the chronic wasting disease (CWD) agent to white-tailed deer by intravenous blood transfusion
Author links open overlay panel Najiba Mammadova ab Eric Cassmann ab Justin J.Greenlee
https://doi.org/10.1016/j.rvsc.2020.10.009 Get rights and content
Under a Creative Commons licenseopen access
Highlights
•The chronic wasting disease (CWD) agent efficiently transmits between white-tailed deer.
•Blood from CWD infected deer contains infectious prions.
•A single intravenous blood transfusion resulted in CWD transmission with an incubation of 25.6 months for the GG96 recipient.
•The GS96 recipient had a longer incubation of 43.6 months.
Abstract
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSEs) that affects free-ranging and captive cervid species. The infectious agent of CWD may be transmitted from ingestion of prions shed in bodily fluids (e.g. feces, urine, saliva, placenta tissue) of infected animals, contaminated pastures, and/or decomposing carcasses from dead animals. Studies have also demonstrated prion infectivity in whole blood or blood fractions of CWD infected animals. To determine if CWD-infected blood contained sufficient levels of prion infectivity to cause disease, recipient deer were inoculated intravenously (IV) with blood derived from a CWD-infected white-tailed deer. We found that the CWD agent can be successfully transmitted to white-tailed deer by a single intravenous blood transfusion. The incubation period was associated with recipient prion protein genotype at codon 96 with the GG96 recipient incubating for 25.6 months and the GS96 recipient incubating for 43.6 months. This study complements and supports an earlier finding that CWD can be transmitted to deer by intravenous blood transfusion from white-tailed deer with CWD.
snip...
This study complements and reinforces earlier findings that CWD can be transmitted to deer by intravenous blood transfusion from white-tailed deer with CWD (Mathiason et al., 2010; Mathiason et al., 2006). In a previous study, a group of eight, 6-month-old fawns were IV inoculated with ~250 mL of whole blood derived from experimentally IC inoculated CWD positive white-tailed deer (Mathiason et al., 2010). In this study, all eight deer were determined to be CWD positive by IHC of all relevant tissues, and began to show clinical signs of TSE between 15 and 26 months post inoculation (Mathiason et al., 2010). While similar results were obtained in our study, we determined that only 100 mL of CWD-infected blood contained sufficient levels of prion infectivity to cause disease compared to the 250 mL of whole blood used by Mathiason et al. (Mathiason et al., 2010). In an earlier study, a cohort of three 6-month-old white-tailed deer fawns were exposed to the agent of CWD via either a single intraperitoneal (IP) inoculation (n = 2) or an IV transfusion (n = 1) of blood derived from a naturally infected CWD positive mule deer (Mathiason et al., 2006). Similar to our findings, the fawn that received blood via IV transfusion had detectable PrPSc in the CNS (medulla at the level of the obex), tonsil, and retropharyngeal lymph nodes (Mathiason et al., 2006); however, it did not present with clinical signs and was euthanized 18 months post inoculation (Mathiason et al., 2006).
We demonstrate here that the CWD agent can be successfully transmitted to white-tailed deer by a single intravenous blood transfusion from CWD-infected white-tailed deer. The incubation period appeared to be associated with recipient genotype with the GG96 deer (940) incubating for 25.6 months, while the GS96 deer (941) incubated for 43.6 months; however, we take into consideration the limitation of the small sample size in this study. While a previous and larger study showed similar results, we determined that only 100 mL of CWD-infected blood (~2.5 times less than previously shown in (Mathiason et al., 2010)) contained sufficient levels of prion infectivity to cause disease. The identification of blood-borne transmission of the CWD agent is important in reinforcing the risk of exposure to CWD via blood as well as the possibility of hematogenous transmission of the CWD agent through insect vector. Finally, these results further highlight the importance of developing a sensitive and reproducible blood-based test to detect pre-clinical CWD, and warrant the continued advancement and evaluation of sensitive antemortem diagnostic tests for the detection of PrPSc in blood of asymptomatic cervids early in the incubation period.
Research Project: Pathobiology, Genetics, and Detection of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research
Title: Successful transmission of the chronic wasting disease (CWD) agent to white-tailed deer by intravenous blood transfusion
Author item MAMMADOVA, NAJIBA - Orise Fellow item CASSMAN, ERIC - Orise Fellow item Greenlee, Justin Submitted to: Research in Veterinary Science Publication Type: Peer Reviewed Journal Publication Acceptance Date: 10/14/2020 Publication Date: 12/20/2020 Citation: Mammadova, N., Cassman, E., Greenlee, J.J. 2020. Successful transmission of the chronic wasting disease (CWD) agent to white-tailed deer by intravenous blood transfusion. Research in Veterinary Science. 133:304-306. https://doi.org/10.1016/j.rvsc.2020.10.009. DOI: https://doi.org/10.1016/j.rvsc.2020.10.009 Interpretive Summary: Chronic wasting disease (CWD) is a fatal disease of cervids that causes damaging changes in the brain. The infectious agent is an abnormal protein called a prion that has misfolded from its normal state. Chronic wasting disease may be transmitted from ingestion of prions shed in bodily fluids (e.g. feces, urine, saliva, placenta tissue) of infected animals. Few studies have also reported detection of infectious prions in blood. To determine if CWD-infected blood can transmit prion disease, recipient deer were inoculated intravenously (IV) with blood derived from a CWD-infected white-tailed deer. We found that two out of three animals developed disease. This study complements and supports an earlier finding that CWD can be transmitted to deer by intravenous blood transfusion from white-tailed deer with CWD. This information is useful to wildlife and agricultural officials that are involved in efforts to control the spread of chronic wasting disease.
Technical Abstract: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSEs) that affects free-ranging and captive cervid species. The infectious agent of CWD may be transmitted from ingestion of prions shed in bodily fluids (e.g. feces, urine, saliva, placenta tissue) of infected animals, contaminated pastures, and/or decomposing carcasses from dead animals. Studies have also demonstrated prion infectivity in whole blood or blood fractions of CWD infected animals. To determine if CWD-infected blood contained sufficient levels of prion infectivity to cause disease, recipient deer were inoculated intravenously (IV) with blood derived from a CWD-infected white-tailed deer. We found that the CWD agent can be successfully transmitted to white-tailed deer by a single intravenous blood transfusion with a mean incubation period of approximately 35 months and an attack rate of 100%. This study complements and supports an earlier finding that CWD can be transmitted to deer by intravenous blood transfusion from white-tailed deer with CWD.
Thursday, June 3, 2021
CWD TSE PRION ZOONOSIS TRANSMISSION TO HUMANS BY BLOOD TRANSFUSION, iatrogenic CJD, WHAT IF?
FRIDAY, JUNE 04, 2021
Texas Breeder Deer May Have Spread Brain Disease CWD TSE Prion Into The Wild
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
4:06 PM
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