Emergence of CWD strains

Chronic wasting disease (CWD) strains present a novel challenge to defining and mitigating this contagious prion disease of deer, elk, moose, and reindeer. Similar to strains of other prion diseases (bovine spongiform encephalopathy, sheep scrapie), CWD strains can affect biochemical and neuropathological properties of the infectious agent, and importantly interspecies transmission. To date, ten CWD strains have been characterized. The expanding range of CWD in North America and its presence in South Korea as well as Scandinavian countries will potentially result in millions of cervids infected with CWD; thus, novel strains will continue to emerge. In this review, we will summarize the characteristics of known CWD strains and describe the impact of prion protein gene polymorphisms on the generation of strains. We will also discuss the evidence that individual cervids can harbor more than one CWD strain, complicating strain analysis, and affecting selection and adaptation of strains in new hosts

Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles

Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite (Mte) retain infectivity following intracerebral inoculation. Here, we assess the oral infectivity of Mte- and soil-bound prions. We establish that prions bound to Mte are orally bioavailable, and that, unexpectedly, binding to Mte significantly enhances disease penetrance and reduces the incubation period relative to unbound agent. Cox proportional hazards modeling revealed that across the doses of TSE agent tested, Mte increased the effective infectious titer by a factor of 680 relative to unbound agent. Oral exposure to Mte-associated prions led to TSE development in experimental animals even at doses too low to produce clinical symptoms in the absence of the mineral. We tested the oral infectivity of prions bound to three whole soils differing in texture, mineralogy, and organic carbon content and found soil-bound prions to be orally infectious. Two of the three soils increased oral transmission of disease, and the infectivity of agent bound to the third organic carbon-rich soil was equivalent to that of unbound agent. Enhanced transmissibility of soil-bound prions may explain the environmental spread of some TSEs despite the presumably low levels shed into the environment. Association of prions with inorganic microparticles represents a novel means by which their oral transmission is enhanced relative to unbound agent

Prions Adhere to Soil Minerals and Remain Infectious

An unidentified environmental reservoir of infectivity contributes to the natural transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) in sheep, deer, and elk. Prion infectivity may enter soil environments via shedding from diseased animals and decomposition of infected carcasses. Burial of TSE-infected cattle, sheep, and deer as a means of disposal has resulted in unintentional introduction of prions into subsurface environments. We examined the potential for soil to serve as a TSE reservoir by studying the interaction of the disease-associated prion protein (PrP(Sc)) with common soil minerals. In this study, we demonstrated substantial PrP(Sc) adsorption to two clay minerals, quartz, and four whole soil samples. We quantified the PrP(Sc)-binding capacities of each mineral. Furthermore, we observed that PrP(Sc) desorbed from montmorillonite clay was cleaved at an N-terminal site and the interaction between PrP(Sc) and Mte was strong, making desorption of the protein difficult. Despite cleavage and avid binding, PrP(Sc) bound to Mte remained infectious. Results from our study suggest that PrP(Sc) released into soil environments may be preserved in a bioavailable form, perpetuating prion disease epizootics and exposing other species to the infectious agent

Effects of Elk-PrPC expression levels on CWD strain properties

Chronic Wasting Disease (CWD) is a contagious prion disease affecting various species of free-ranging and/or captive cervids on three continents. Species-specific prion protein (PrPC) polymorphisms influence prion conversion into PrPCWD. PrPC amino acid variation can also regulate disease susceptibility to particular prion strains and has been implicated in the diversification of prion strain conformers [1, 2, 3]. Elk and deer PrPC differ at residue E226Q and this amino acid difference has been implicated in the selection of CWD1 and CWD2 prion strains [4]. As PrPC expression has been suggested to affect prion strain evolution [5], we hypothesized that elk PrPC levels affect CWD strain generation. To test this hypothesis, transgenic (tg) FVB mice over-expressing elk PrPC [6] were crossed with prnp knock-out FVB mice to generate tg-elk with different PrPC expression levels. Both tg-elk+/+ and tg-elk± were exposed to white-tailed deer CWD strains (Wisc-1 and H95+) [2, 3]. The H95+ strain was a mixture generated on passage of Wisc-1 in deer heterozygous for H95G96 and Q95S96 [2]. Tg-elk+/+ mice succumbed to Wisc-1 with a mean incubation period of 116 ± 7 days post infection (dpi) compared to 164 ± 11 dpi for the H95+ strain mixture. Consistent with the reduced PrPC expression, the same deer prion strains resulted in longer incubation periods (157 ± 21 dpi and >180 dpi, respectively) when passaged in tg-elk± mice. After first passage, transmission of Wisc-1 and H95+ in tg-elk+/+ mice resulted in a single neuropathological profile that differed from the profile produced by passage of elk prions (described as the CWD2 strain [1]). Our results show that, upon first passage, the E226Q polymorphism did not affect the strain properties of deer prions and indicates a single strain (Wisc-1) was selected by the tg-elk+/+ mice. The comparative analysis of neuropathological profiles between high and low expression tg-elk on first and second passage will be presented

Susceptibility of Beavers to Chronic Wasting Disease

Chronic wasting disease (CWD) is a contagious, fatal, neurodegenerative prion disease of cervids. The expanding geographical range and rising prevalence of CWD are increasing the risk of pathogen transfer and spillover of CWD to non-cervid sympatric species. As beavers have close contact with environmental and food sources of CWD infectivity, we hypothesized that they may be susceptible to CWD prions. We evaluated the susceptibility of beavers to prion diseases by challenging transgenic mice expressing beaver prion protein (tgBeaver) with five strains of CWD, four isolates of rodent-adapted prions and one strain of Creutzfeldt–Jakob disease. All CWD strains transmitted to the tgBeaver mice, with attack rates highest from moose CWD and the 116AG and H95+ strains of deer CWD. Mouse-, rat-, and especially hamster-adapted prions were also transmitted with complete attack rates and short incubation periods. We conclude that the beaver prion protein is an excellent substrate for sustaining prion replication and that beavers are at risk for CWD pathogen transfer and spillover. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Chronic wasting disease prions in mule deer interdigital glands

Chronic wasting disease (CWD) is a geographically expanding, fatal neurodegenerative disease in cervids. The disease can be transmitted directly (animal-animal) or indirectly via infectious prions shed into the environment. The precise mechanisms of indirect CWD transmission are unclear but known sources of the infectious prions that contaminate the environment include saliva, urine and feces. We have previously identified PrPC expression in deer interdigital glands, sac-like exocrine structures located between the digits of the hooves. In this study, we assayed for CWD prions within the interdigital glands of CWD infected deer to determine if they could serve as a source of prion shedding and potentially contribute to CWD transmission. Immunohistochemical analysis of interdigital glands from a CWD-infected female mule deer identified disease-associated PrPCWD within clusters of infiltrating leukocytes adjacent to sudoriferous and sebaceous glands, and within the acrosyringeal epidermis of a sudoriferous gland tubule. Proteinase K-resistant PrPCWD material was amplified by serial protein misfolding cyclic amplification (sPMCA) from soil retrieved from between the hoof digits of a clinically affected mule deer. Blinded testing of interdigital glands from 11 mule deer by real-time quake-induced conversion (RT-QuIC) accurately identified CWD-infected animals. The data described suggests that interdigital glands may play a role in the dissemination of CWD prions into the environment, warranting future investigation

Water-fat magnetic resonance imaging of adipose tissue compartments in the normal third trimester fetus

BACKGROUND: Assessment of fetal adipose tissue gives information about the future metabolic health of an individual, with evidence that the development of this tissue has regional heterogeneity. OBJECTIVE: To assess differences in the proton density fat fraction (PDFF) between fetal adipose tissue compartments in the third trimester using water-fat magnetic resonance imaging (MRI). MATERIALS AND METHODS: Water-fat MRI was performed in a 1.5-T scanner. Fetal adipose tissue was segmented into cheeks, thorax, abdomen, upper arms, forearms, thighs and lower legs. PDFF and R2* values were measured in each compartment. RESULTS: Twenty-eight women with singleton pregnancies were imaged between 28 and 38 weeks of gestation. At 30 weeks\u27 gestation (n=22), the PDFF was statistically different between the compartments (P CONCLUSION: Fetal adipose tissue accumulates lipids at a similar rate in all white adipose tissue compartments. PDFF variances between the compartments suggest that accumulation begins at different gestational ages, starting with cheeks, followed by extremities, trunk and abdomen. Additionally, MRI was able to detect differences in the PDFF between fetal brown adipose tissue and white adipose tissue

Cellular prion protein distribution in the vomeronasal organ, parotid, and scent glands of white-tailed deer and mule deer

Chronic wasting disease (CWD) is a contagious and fatal transmissible spongiform encephalopathy affecting species of the cervidae family. CWD has an expanding geographic range and complex, poorly understood transmission mechanics. CWD is disproportionately prevalent in wild male mule deer and male white-tailed deer. Sex and species influences on CWD prevalence have been hypothesized to be related to animal behaviours that involve deer facial and body exocrine glands. Understanding CWD transmission potential requires a foundational knowledge of the cellular prion protein (PrPC) in glands associated with cervid behaviours. In this study, we characterized the presence and distribution of PrPC in six integumentary and two non-integumentary tissues of hunter-harvested mule deer (Odocoileus hemionus) and white-tailed deer (O. virginianus). We report that white-tailed deer expressed significantly more PrPC than their mule deer in the parotid, metatarsal, and interdigital glands. Females expressed more PrPC than males in the forehead and preorbital glands. The distribution of PrPC within the integumentary exocrine glands of the face and legs were localized to glandular cells, hair follicles, epidermis, and immune cell infiltrates. All tissues examined expressed sufficient quantities of PrPC to serve as possible sites of prion initial infection, propagation, and shedding

The Future Direction of Inter-Professional Education in Ireland: Insights From Focus Groups With Key Stakeholders

Rationale: An inter-professional education (IPE) masterclass symposium titled, ‘The journey to team-based healthcare’, was jointly hosted by the School of Pharmacy, Royal College of Surgeons in Ireland (RCSI), the Irish Institute of Pharmacy and the Bill Gatton College of Pharmacy in East Tennessee State University in May 2017. The masterclass provided a comprehensive overview of IPE initiatives based on the extensive experience of senior academics from the host institutions, which included staff from pharmacy, nursing and medicine. The masterclass was attended by healthcare professionals, policy makers and educationalists working in Ireland. As part of the symposium, focus groups were conducted with a sample of symposium attendees to determine their opinions and perceptions, as key stakeholders, regarding the development, implementation and future direction of IPE in Ireland. Methods: Focus groups were conducted with symposium attendees using a topic guide that was developed based on previous literature. Questions explored participants’ views and experiences on a range of topics including development and implementation of IPE activities, and key priorities for developing future IPE initiatives. Thematic analysis was conducted to identify key themes. Findings: Three focus groups were conducted each involving five to six participants (total 16 participants: nine female). Preliminary themes have been identified and further analysis is ongoing. Discussion/conclusion: The research findings will help to inform the future development and direction of IPE initiatives at both undergraduate and postgraduate level within the host institutions and could help in the development of an IPE strategy for undergraduate and post-graduate teaching across Ireland

Reliability of Routinely Collected Hospital Data for Child Maltreatment Surveillance

Background: Internationally, research on child maltreatment-related injuries has been hampered by a lack of available routinely collected health data to identify cases, examine causes, identify risk factors and explore health outcomes. Routinely collected hospital separation data coded using the International Classification of Diseases and Related Health Problems (ICD) system provide an internationally standardised data source for classifying and aggregating diseases, injuries, causes of injuries and related health conditions for statistical purposes. However, there has been limited research to examine the reliability of these data for child maltreatment surveillance purposes. This study examined the reliability of coding of child maltreatment in Queensland, Australia. Methods: A retrospective medical record review and recoding methodology was used to assess the reliability of coding of child maltreatment. A stratified sample of hospitals across Queensland was selected for this study, and a stratified random sample of cases was selected from within those hospitals. Results: In 3.6% of cases the coders disagreed on whether any maltreatment code could be assigned (definite or possible) versus no maltreatment being assigned (unintentional injury), giving a sensitivity of 0.982 and specificity of 0.948. The review of these cases where discrepancies existed revealed that all cases had some indications of risk documented in the records. 15.5% of cases originally assigned a definite or possible maltreatment code, were recoded to a more or less definite strata. In terms of the number and type of maltreatment codes assigned, the auditor assigned a greater number of maltreatment types based on the medical documentation than the original coder assigned (22% of the auditor coded cases had more than one maltreatment type assigned compared to only 6% of the original coded data). The maltreatment types which were the most ‘under-coded’ by the original coder were psychological abuse and neglect. Cases coded with a sexual abuse code showed the highest level of reliability. Conclusion: Given the increasing international attention being given to improving the uniformity of reporting of child-maltreatment related injuries and the emphasis on the better utilisation of routinely collected health data, this study provides an estimate of the reliability of maltreatment-specific ICD-10-AM codes assigned in an inpatient setting