The 2011 Prion Conference was held in Montreal earlier this year, showcasing some of the encouraging new studies and findings taking place in TSE research and we thought it a great opportunity to share some of these finding with you.
Transmissible spongiform encephalopathies (TSEs) are infectious, chronic, progressive and fatal neurodegenerative disorders that affect different species. TSEs vary amongst species and the exact mechanisms of transmission and infection remain largely unclear. One fact that does hold true is that TSEs are linked to a type of protein called Prions, self-propagating forms of protein found in cells within the body. There is much on-going research into the control of TSEs including those causing Scrapie and Chronic Wasting Disease. Scrapie and CWD TSEs are slightly unique from others in that they are transmitted horizontally through direct animal contact or contact with an infected environment, and they manifest as endemic infection (confined to a particular area) as opposed to the epidemic infections (extremely prevalent and widespread) associated with BSE.
Wathne et al (2011), suggest that oral transmission, for example through saliva?, of scrapie is the most common route of infection and lesions to the skin or mucosa will facilitate this transmission. The findings of Denkers et al (2011) concurrently with those of Seelig et al (2011) support this theory and propose that as part of their natural foraging nature, cervids likely experience minor oral lesions and abrasions that impact their susceptibility to prion entry and subsequent infection. Haley et al (2011) claim that infectious prions of cervids shed through saliva, urine and feces lending to their contamination of commonly inhabited environment. In scrapie research in sheep and goats, Lowe et al (2011) theorize that prions can replicate to higher levels in olfactory neurons in the nasal mucosa because of the neuron-rich environment of that sensory epithelium, and that any later damage to the mucosa as the result of injury, inflammation or infection can accelerate prion release into nasal secretions. The development and use of a new protein misfolding cyclic amplification (PMCA) technique is allowing for prion detection in various tissues and secretions such as milk, feaces, urine, saliva, mucous and blood at much lower levels of infection than could previously be detected. Perfection and recognition of this technique could become a useful tool for disease detection in the future.
Research into prion contaminated environments continues with some fairly consistent findings. Kuznetsora et al (2011) claim that soil can serve as a stable reservoir for infectious prion proteins and that soil types like clay based earth can enhance prion infectivity where soils like quartz sands bind PrPSc (abnormal prion protein associated with TSEs) less avidly. Smith (2011) supports the finding of lasting prion contamination of soil with very little reduction in titre over time but added that there is also very little migration of TSE through the soil. Nagaoka et al (2011) disagree slightly with these findings, having found a decrease in soil PrPSc levels over a 6 month period. Both camps agree that more research is necessary for the sake of accuracy.
Beyond the on-going research into prion transmission and mechanism of infection, much work is being done on the immunity or resistance to TSEs in sheep, goats and cervids. The facile horizontal transmission of these diseases and the clear agreement that natural shedding and environmental contamination are commonplace beg the question; why have the diseases not completely taken over the industry? Although no natural immunity to prion exposure has been found, existing and emerging research shows an influence of genotype on the effect of the disease. The identification of specific scrapie-resistant genotypes in sheep are quite clearly defined and commonly used in disease control programs throughout the world including some pathways in Canada’s Scrapie Flock Certification Program. A study by Hurtado et al (2011) suggests that statistical analysis of data has shown a protective role of certain genotypes of goats against classical scrapie. Fast et al (2011) support the influence of the goat genotype on the susceptibility to a TSE infection and further claim that there is a clear influence of the goat genotype on the susceptibility to BSE, with K222 genotype goats being far less susceptible. The European goat-BSE consortium is using these genotype tools to further eradicate the disease by breeding for TSE resistance in goats (Langeveld et al, 2011). Similar cervid based research has shown that certain homozygous genotype white-tailed deer have a 4 time greater risk of CWD infection where their heterozygous genotype counterparts survive CWD infection 49% longer, living an additional 8.25 months on average. Common to all of the TSE diseases is the realization that prion variation influences the susceptibility to and progression of the disease in an individual. Gonzalez et al (2011) suggest that natural scrapie agents consist of a mixture of strains that are differentially propagated in sheep of varying genotypes, further lending to the complexity of genotype resistance.
One common thread through all branches of TSE research is that a quality disease control program will be multifaceted. While breeding for TSE resistance can be a useful tool in controlling infection rates, there is of yet no full-proof genetic method of eliminating disease. Eradication of TSE can be obtained while maintaining a certain level of all genotypes, thereby allowing the continuance of genetic diversity (Langeveld et al, 2011). Limiting exposure to infectious animals and environment are fundamental in controlling the spread of the disease but are further complicated by the lengthy incubation period and opportunistic nature of the prion. Long term disease control commitment and monitoring continue to be pivotal in TSE disease control and eradication.
Denkers et al, 2011. Minor Oral Lesions Facilitate CWD Infection. Proceedings from Prion 2011. Montreal.
Haley et al, 2011. Detection of CWD Prions in Urinary, Salivary, and Intestinal Tissues of Deer: Potential Mechanisms of Prion Shedding and Transmission. Proceedings from Prion 2011. Montreal.
Hurtado et al, 2011. Prion Protein Gene Polymorphisms in Spanish Goat and Their Association with Classical and/or Atypical Scrapie. Proceedings from Prion 2011. Montreal.
Kuznetsova et al, 2011. Soil Properties as a Factor in CWD Spread in Western Canada. Proceedings from Prion 2011. Montreal.
Langeveld et al, 2011. State of the Art and Perspectives for Genetic Eradication of TSEs in Sheep and Goats. Proceedings from Prion 2011. Montreal.
Lowe et al, 2011. Accelerated Prion Shedding Following Damage to the Olfactory Epithelium. Proceedings from Prion 2011. Montreal.
Nagaoka et al, 2011. Sensitive Detection of Scrapie Prion Protein in Soil. Proceedings from Prion 2011. Montreal.
Seelig et al, 2011. Identification of PrPCWD in the Salivary Gland Epithelium of White-tailed Deer: Novel Insights Into Mechanisms of CWD Horizontal Transmission. Proceedings from Prion 2011. Montreal.
Smith. A, 2011. High Survival Rates of TSE Infectivity Buried in Two Soil Types. Proceedings from Prion 2011. Montreal.
Wathne et al, 2011. Involvement of Skin DC Subsets in TSE Transmission. Proceedings from Prion 2011. Montreal.