Microb Risk Anal . 2020 Aug 15;100134. doi: 10.1016/j.mran.2020.100134. Online ahead of print.
Assessing the aggregated probability of entry of a novel prion disease agent into the United Kingdom
Verity Horigan 1, Paul Gale 1, Amie Adkin 1, Timm Konold 2, Claire Cassar 2, John Spiropoulos 2, Louise Kelly 1 3 Affiliations expand PMID: 32837979 PMCID: PMC7428426 DOI: 10.1016/j.mran.2020.100134
Free PMC article
Abstract
In 2018 prion disease was detected in camels at an abattoir in Algeria for the first time. The emergence of prion disease in this species made it prudent to assess the probability of entry of the pathogen into the United Kingdom (UK) from this region. Potentially contaminated products were identified as evidenced by other prion diseases. The aggregated probability of entry of the pathogen was estimated as very high and high for legal milk and cheese imports respectively and very high, high and high for illegal meat, milk and cheese products respectively. This aggregated probability represents a qualitative assessment of the probability of one or more entry events per year into the UK; it gives no indication of the number of entry events per year. The uncertainty associated with these estimates was high due to the unknown variation in prevalence of infection in camels and an uncertain number and type of illegal products entering the UK. Potential public health implications of this pathogen are unknown although there is currently no evidence of zoonotic transmission of prion diseases other than bovine spongiform encephalopathy to humans.
Keywords: Aggregated probability; Entry assessment; Prion agent.
Crown Copyright © 2020 Published by Elsevier B.V. All rights reserved.
Conflict of interest statement None.
1. Introduction
Prion diseases, or transmissible spongiform encephalopathies (TSEs), are progressive neurodegenerative disorders that affect both humans and animals and are characterised by long incubation periods frequently of many years. Such disorders are biochemically characterised by conversion of a normal cellular form of the prion protein (PrPc ) into a misfolded disease associated form (PrPSc) that accumulates into amyloid protein aggregates in the brain (Norrby, 2011).
Scrapie in sheep was the first animal TSE to be described in the 18th century in Great Britain but TSEs have since been detected in a number of species, including scrapie in goats, chronic wasting disease (CWD) in deer and bovine spongiform encephalopathy (BSE) in cattle. The BSE crisis led to the slaughter of 3.3 million cattle and an estimated economic loss of £3.7 billion in the United Kingdom (UK) (Beck et al., 2007). It is believed that BSE crossed the species barrier to humans through the consumption of contaminated beef and bovine products during the 1990s (ECDC 2017) and that this zoonotic transmission of BSE has since led to the death of 178 people with variant CreutzfeldtJakob disease (NCJDRSU 2019). Prion diseases can therefore pose serious risks to both animal and human health and the first detection of a TSE in deer in Europe in 2016 demonstrates the continued need for a global awareness of these diseases (Benestad et al., 2016).
Within the European Union there is a statutory requirement to test for TSEs where disease is suspected and active surveillance systems to test for disease in healthy slaughter animals or fallen stock. However, in countries that do not have active surveillance systems, detection of cases relies on the reporting of clinical suspects where, if the animal keeper or veterinary surgeon are not familiar with the clinical signs, TSEs may not be considered in the differential diagnosis of neurological diseases or other conditions that present with similar signs (Konold and Phelan, 2014). Prion disease has recently been confirmed in three dromedary camels (Camelus dromedarius) from an Algerian slaughterhouse (Babelhadj et al., 2018) after clinical signs compatible with those of TSEs in other species were observed ante mortem. Disease associated pathological changes or prion protein were found in brain by Western blotting, histology, immunohistochemistry (IHC) and paraffin-embedded tissue blot; PrPSc was also detected in the lymph nodes of the one camel tested by IHC.
Information gathered from breeders and slaughterhouse personnel suggests that similar clinical signs had been observed since the 1980s (Babelhadj et al., 2018). Subsequently, the disease has also been reported in a single case of a 12 year old dromedary camel from the region of Tataouine, Tunisia (Agrimi, 2019; OIE bulletin 2019).
There are many knowledge gaps about the biological characteristics of this new TSE, termed camel prion disease (CPD). Detection of infection in lymph nodes of one animal suggests extra-neural pathogenesis and, therefore, potential transmission of CPD between animals similar to that of classical scrapie and CWD. Such transmission of CPD could be facilitated over long distances by the traditional nomadic herding practices of dromedaries and the trade patterns between Algeria and other countries in North Africa and the Middle East (Bouslikhane, 2015). In light of the devastation caused by BSE, and its subsequent zoonotic transmission, CPD was used here to assess the probability of entry of a novel prion disease agent into the UK via livestock and livestock products. The approach used was to assess the aggregated probability, using the number of imports per year to avoid potential under-estimation as has previously been described (Kelly et al., 2018). Of note, the zoonotic potential of the disease is unknown and this assessment is of the probability of introduction of the CPD agent into the UK only, not of any onward transmission to humans or animals.
2. Methods
2.1. Risk question and pathway
The risk question to be addressed was:
‘What is the aggregated probability of entry of the CPD agent into the United Kingdom from North Africa or the Middle East in one year?’
The risk pathway highlighting the probabilities to be considered for potential entry of the CPD agent into the UK is shown in Fig. 1.
The approach used was qualitative and based on the framework set out by the OIE (World Organization for Animal Health) (OIE 2004). The probabilities in Fig. 1 are conditional and were expressed qualitatively as negligible, very low, low, medium, high and very high (EFSA 2006; FAO/ WHO 2009). The qualitative probabilities for each stage of the risk pathway up to, and including, the probability that an infected animal/ animal product is not detected at import (p1, p2, p3, p4, p5) were combined as described previously (Gale et al., 2010) to give the probability of entry of an individual infected animal/product (P). Entry was defined as the probability of entry of a CPD positive animal or contaminated animal product into the UK within one year taking into account the current products which are imported from the regions of interest. For comparison, an aggregated probability of entry (Pa) of all categories of live animals/products was also assessed to provide an annual probability of entry using a graphical reference tool proposed by Kelly et al., (2018). This tool removes some of the subjectivity that is often associated with deriving the annual qualitative probability of entry for animal import risk assessments as it enables the number of units imported to be combined with this individual qualitative event probability. In this way, the reference tool ‘considers various qualitative categories of individual probability and determines the relationship between these probabilities, the number of imports and the annual probability of entry’ (Kelly et al., 2018).
The quantitative bounds for the individual probability correspond to previously published example definitions (FAO/WHO 2009) (Table 1).
Uncertainty associated with the estimates for the probabilities were categorised according to Spiegelhalter and Riesch (2011) depending on availability, completeness and quality of evidence.
Relevant data for use in the risk assessment were scarce. Briefly, the number of camel products imported into the UK from the area of interest was obtained from the EU Trade Control and Expert System (TRACES) where available. Otherwise, the following assumptions were made:
■ The prevalence of CPD in camels in the region of interest - 3.1% (based on Babelhadj et al. (2018))
■ The incidence and prevalence of CPD in camel products, derived from:
Fig. 1.. Risk pathway for the aggregated probability of entry of the CPD agent into the UK in one year.
Table 1 Definitions of the quantitative bounds used to correspond to the qualitative probability (taken from (Chianini et al., 2015)).
snip...
○ Disease progression in camels – similar to scrapie (based on Babelhadj et al. (2018))
○ Relative resistance of CPD associated PrPSc to heat and chemicals – similar to other TSEs (see Results section for references)
○ Correlation of disease presence and PrPSc deposition – similar to other TSEs (see Results section for references)
○ Systemic distribution of disease – similar to scrapie (based on Babelhadj et al. (2018))
■ The number of illegally imported products – based on data on illegal seizures and FAOSTAT production data
■ The number of processed camel products both legally and illegally imported – assumed by the author
A further assumption made was that the aggregated probability calculations used the same quantitative bounds (FAO/WHO 2009) as used in the tool by Kelly et al. (2018). It is acknowledged that this probability could therefore change if these bounds were to be altered.
3. Results
3.1. Risk assessment
3.1.1. Probability camel is infected with camel prion disease in exporting country (p1)
Detection of abnormal neurological signs since the 1980s within a restricted geographical area of Algeria suggests that the expansion of CPD to other areas (and countries) may be restricted or that the disease can remain largely undiagnosed. According to a recent presentation of the Mediterranean Animal Health Network, the disease was also reported in Tunisia and the incidence in the initial region of Algeria was described as ‘rapidly and progressively increasing’ (Agrimi, 2019). It is, therefore, possible that movement of camels has allowed infected animals to enter other countries. Asides from the legal trade of camels, approximately 268 million people in Africa practice some form of pastoralism (Luizza, 2017). For example, over 95% of cross-border trade within the Horn of Africa is unofficial and carried out by nomadic pastoralists trading livestock. Given that disease was first noticed in the 1980s and the nomadic way of life in this area, exporting countries were therefore considered as those making up the regions of North Africa and the Middle East for the purpose of this assessment.
Twenty of 937 camels in 2015 and 51 of 1,322 in 2016 showed neurologic signs at slaughter giving an overall estimated apparent prevalence of 3.1% in dromedaries brought for slaughter (Babelhadj et al., 2018). In the absence of further information including confirmatory testing, an assumption was made that the prevalence of CPD in live camels in the regions of interest was high with high uncertainty because of the lack of testing data from countries other than Algeria and in only 3 camels in Algeria itself.
3.1.2. Probability infected animal is not detected on farm or at slaughter (p2)
Although anecdotal evidence suggests that herdsmen have noticed neurological signs in camels on the farm and at slaughter (Babelhadj et al., 2018) it was assumed that these animals were still being sent for slaughter and entering the food and feed chains. It was also assumed that as the other countries in the regions of interest have not been aware of the presence of this disease that they would not be surveying their animals for clinical signs and therefore animals will still be sent to slaughter. The probability of a camel with CPD not being detected on farm or at slaughter was therefore assumed to be high with low uncertainty.
3.1.3. Probability animal or animal product for export contains the CPD agent given the camel is infected and undetected (p3)
Camel products that can be legally exported to the UK, those for which databases exist to monitor the levels of exports and the probability of containing the CPD agent (given the source camel is infected) of these products are shown in Table 2.
The probability of a commodity containing the CPD agent depends on the presence of infectivity in the live animal and processes the commodity has undergone which may destroy it. As such, the uncertainty associated with this probability for all products was high as a result of knowledge gaps concerning these two factors.
The prion protein, PrPSc, has been shown to accumulate with infectivity and is therefore considered a reliable biochemical marker for infection (Thomzig et al., 2007). PrPSc has been isolated from the muscle tissue, skin, milk and urine of TSE affected animals (Andréoletti et al., 2004; Thomzig et al., 2007; Andréoletti et al., 2011; Buschmann and Groschup, 2005; Chianini et al., 2015;
Table 2
Probability of containing the CPD agent for individual commodities originating from camels including primary and processed products.
Commodity Primary product used Import to the UK allowed from regions of interest
Traceable (source) Probability of containing the CPD agent (uncertainty in brackets)
Live animals
Live camels - No - Certain
Primary products
Meat - No - High (high)
Milk - Yes Yes (Traces) High (high)
Hair - Yes Yes (Traces) Negligible (high)
Urine - No - High (high)
Semen - No - Low (high)
Treated Hides and skins - Yes Yes (Traces) High (high)
Processed products
Soap Milk Yes No Negligible (high)
Lip balm Milk Yes No Negligible (high)
Chocolate Milk Yes No Negligible (high)
Leather products Skin Yes No Very low (high)
Cheese Milk Yes Yes (Traces) High (high)
Bone ornaments Bone Yes No Very low (high)
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Henderson et al., 2015; Konold et al., 2013; Rubenstein et al., 2011) and the pessimistic assumption here is that CPD distribution in a camel is similar to classical scrapie and CWD based on the detection of PrPSc in the lymphatic system (Babelhadj et al., 2018; Haley et al., 2014). It was, therefore, estimated that the probability that a camel meat/milk/urine product contains the CPD agent, given it comes from an infected, undetected animal was high.
The only milk imported from the region of interest to the UK is Ultra-High temperature treated (UHT). This processing involves heating to ∼135-145°C for 1-10 seconds (Deeth, 2004) which is not sufficient to fully destroy prion activity (Franscini et al., 2006; Yoshioka et al., 2013). Similarly for hides/skins, if they are not treated with a transformation process with a proven capacity to reduce TSE infectivity (Scientific Steering Committee 2000), then it is considered unlikely that the CPD agent would be destroyed. The probability of UHT milk and hides/skins containing the CPD agent, was therefore estimated as high.
The European Food Safety Authority (EFSA) considered the risk of TSE transmission associated with semen and embryos collected from classical scrapie incubating sheep and goats to range from negligible to low (EFSA Panel on Biological Hazards (BIOHAZ) 2010). PrPSc in semen from a scrapie affected ram has been reported (Rubenstein et al., 2012) so the probability of semen from infected undetected camels containing the CPD agent was estimated to be low (worst case assumption based on the EFSA opinion). For hair PrPSc has been detected in the fibres of the follicular neural network and in the hair follicle isthmus in hamsters but not in the outer root sheet cells or the bulb region (Thomzig et al., 2007). The probability of camel hair being infected with the CPD agent was therefore assumed to be negligible given the lack of evidence for PrPSc in the cells of the hair.
Soap products are described as containing ∼ 25% raw camel milk and use a saponifying agent which starts the process of turning the raw ingredients into soap. This agent is usually 100% sodium hydroxide which is known to inactivate PrPSc at a concentration of 0.1M (Käsermann and Kempf, 2003). The probability of soap products and lip balm retaining the CPD agent was therefore estimated to be negligible. Chocolate products manufactured using camel milk can contain ∼ 21% pure camel milk powder. Milk powder production involves spray drying milk in a flow of hot air between 180°C to 220°C (Consulting, W.D. 2019), sufficient to destroy prion activity (Somerville and Gentles, 2011). The probability of chocolate being infected with the CPD agent was thus estimated to be negligible. Camel milk does not curdle readily so camel cheese is traditionally consumed in fresh or fermented form. Fermentation is not expected to reduce the levels of infectivity so the probability of cheese from infected undetected animals being infected with the CPD agent was estimated to be high.
Products made from treated skins/hides from infected animals are assumed to have undergone a tanning process whereby the use of strong alkali and acid solutions will reduce the level of TSE infectivity (Appel et al., 2006; Hughson et al., 2016; Käsermann and Kempf, 2003). The probability of infection was therefore assumed to be very low. Similarly, although experimental evidence has demonstrated TSE infectivity in bone marrow (Huor et al., 2017; Seelig et al., 2010), during the process of cleaning bones for use in processed products such as jewellery it is assumed that the bone marrow is removed. The probability of camel bones being infected with the CPD agent, given an animal is infected, was therefore assumed to be very low.
3.1.4. Probability prion in live animal or animal product survives journey to the UK (p4) and is not detected at import (p5)
The probability of prions remaining infectious throughout the journey to the UK was assumed to be high with low uncertainty for all products for both legal and illegal routes due to the characteristic resistance of PrPSc to both chemical and physical degradation (Taylor, 1999) and evidence of its long term survival (Brown and Gajdusek, 1991; Georgsson et al., 2006). There are no gross lesions suggestive of TSE infection in animal products. There are also no post import tests for TSEs in either legal milk imports or illegal seizures. The probability of CPD infectivity not being detected on import to the UK was therefore assumed to be high with low uncertainty for all products for both legal and illegal routes. Additionally, the annual proportion of searched luggage among the total number of passengers entering a European country (Switzerland) has been estimated at between 0.06% and 0.24% (Jansen et al., 2016). If this is applied to the UK then it suggests that the probability of an illegally imported infected animal product not being detected at import is high.
The probability of CPD not being detected in a live animal was considered to be medium as detection will depend on several factors including the animal showing clinical signs of TSE infection and the signs being correctly diagnosed as TSE by the veterinary inspector. The age of the animal and the progression of clinical disease will also be relevant. The uncertainty associated with this estimate was low.
3.1.5. Probability of entry of the CPD agent in an individual animal/ product into the UK (P)
The probability of entry of the CPD agent in an individual animal/ product into the UK was calculated by combining the probabilities in the risk pathway as described previously (Gale et al., 2010). Results are summarised in Table 3 for both legal and illegal routes of entry for live animals and products.
3.1.6. Number of units imported into the UK per year (n)
Legal exports of live camels, camel meat (including untreated hides), urine and semen from the regions of interest to the UK are prohibited (Table 2). There were no imports of treated hides from camels from the region of interest recorded for the period 2010 to 2016 but, as such imports are permitted, the number of treated hides being exported to the UK was estimated to be within the range of 0 - 1. Since 2010 there has only been one possible consignment of ‘hair’ of species ‘other’ so may not have been of camel origin but an estimate of 1 unit was used here.
The Traces database has details of the volumes of milk and milk products imported into the UK. Approximately 10,830 kg of UHT milk products (it is assumed that the average product is 1 litre in size or 1 kg in weight giving a total of 10,830 units) and 11 Kg (equivalent to 22 units based on a 500g product) of cheese were exported to the UK in one year.
For processed products, soap, lip balm and milk chocolate made from camel milk are available in the UK via the internet or instore. Camel bone jewellery and ornaments and leather goods are also available for sale via the internet. It is assumed that these are all niche products with a limited market and the number of units of each product imported into the UK was estimated to be 1,000.
For illegal imports, data on illegal seizures were used to estimate the number of camel meat and dairy products illegally entering the UK. Illegal imports of red meat and dairy products are not categorised by species so, as a proxy for this, data (FAOSTAT) on the production of animals in the regions of interest were used to predict what percentage of each category would be a camel product. For 2016, camel meat contributed 4.7% to production of all red meat species and camel milk represented 0.47% of whole milk production (FAOSTAT) in the regions of interest. It is unknown whether the illegal milk/milk products seized would have undergone any heat treatment, but as stated above, UHT would not destroy infection. Using the illegal seizure data and FAOSTAT production data it was estimated that 242 units (200g products) of camel meat, 19 units (1Kg product) of milk and 20 units (500g product) of cheese illegally enter the UK in one year.
The number of illegal imports of treated skins/hides and hair was estimated to be between 0 -100 due to the size of the commodity and the low value placed on camel skins in the region of interest. The same figure was used for camel urine which has been used as a traditional medicine since ancient times (Abdel Gader and Alhaider, 2016) so it is possible that passengers entering the UK could illegally import camel urine for medicinal purposes.
For semen, there are difficulties associated with the application of artificial insemination in camelids in particular the collection and handling of semen due to the viscous nature of the seminal plasma (Skidmore, 2018). Therefore the estimate for the number of illegal camel semen straws imported to the UK was between 1-10. The illegal import of batches of camel hair was also estimated to be between 1 - 10 due to the low value placed on camel hair in the region of interest.
The number of illegal imports of all processed products was esti - mated to be between 0 - 1000 assuming these are luxury products aimed at a niche export market.
3.1.7. Aggregated probability of entry of the CPD agent into the UK from North Africa or the Middle East per year (Pa)
The aggregated annual probability of entry of the CPD agent was estimated using the number of units of animals/products imported per year where known (or estimated by the authors where unknown) and the qualitatively assessed probability of entry for an individual infected product (Table 3) using the graphical framework described by Kelly et al., (2018).
For legal imports, the aggregated probability of entry was negligible for livestock, camel meat, urine and semen as these products are pro - hibited (Table 4). The probability was also negligible for hair, soap, lip balm and chocolate based on the assumed lack of infectivity in these products and the number of products imported. For cheese and UHT milk the probability of at least one infected unit entering the UK per year was high and very high respectively. The individual probability per unit for UHT milk increased from high to an aggregated probability of very high as a result of the number of units imported (>10
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) in one year.
The number of units per product illegally imported to the UK was estimated by the authors due to lack of data. This resulted in a range of probabilities for some products, from negligible if no items were im - ported to very high if 100 products were imported (treated hides/skins, urine) (Table 5). Milk products and cheese both had a high probability of entry and camel meat had a very high probability based on the es - timated number of products imported.
4. Discussion
This assessment used the example of CPD to address the probability of entry of a novel prion agent into the UK. The estimated probability per unit was aggregated to take into account the number of units of each product imported per year. Thus the predicted probability is the probability of entry of one or more (i.e. at least one) infected unit per year into the UK. The predicted aggregated probability for legal imports was highest for UHT milk products and cheese whilst for treated hides and skins it was estimated to range from negligible to high depending on whether any units were imported in one year. For illegally imported meat, milk and cheese products the aggregated probability of at least one entry event per year was estimated as very high, high and high respectively. If testing were to be carried out to negate the presence of CPD in the camel population used to produce milk legally exported to the UK then the annual probability of entry would be reduced to neg - ligible. Similarly, as the aggregated probability is based on an example of assumed quantitative bounds (FAO/WHO 2009), were these bounds to be changed then the aggregated probability could also change.
The estimates of probability are associated with high uncertainty throughout the risk pathway hinging, in particular, on the application of a blanket prevalence of CPD within the camel population. The Middle East Respiratory syndrome coronavirus (MERS-CoV) provides an example of an undetected pathogen in camels which, once identi - fied, has since been detected throughout much of the regions of interest suggesting that movement of camels has provided a route of incursion of the virus to different countries (Haagmans et al., 2014; Meyer et al., 2014; Reusken et al., 2013; Reusken et al., 2014). It is possible that
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transmission of CPD between animals could have similarly been facilitated by movement of infected live animals although the disease has currently only been described in a restricted geographical area of Algeria and Tunisia. The involvement of lymphoid tissue, observed in both the Algeria and Tunisia cases, is suggestive of a peripheral pathogenesis, similar to scrapie and CWD in which horizontal transmission occurs efficiently under natural conditions (OIE bulletin 2019). The uncertainty is compounded by lack of data on the epidemiology of CPD. As of June 2020, there is no publically available up-to-date information with regards to the prevalence of CPD in the area of interest or whether additional cases have been detected. The OIE Scientific Commission has called for the collection of further scientific evidence in countries with dromedary camel populations to measure the impact of the disease (OIE bulletin 2019). This could influence the results of the risk assessment should an increase in the incidence of CPD have occurred.
The import of animal products in travellers’ personal consignments presents a considerable risk of introducing infectious agents (Simons et al., 2016; Falk et al., 2013; Hartnett et al., 2007). Analysis from a study on illegal seizures of airline passengers in Germany, found that seizures are typically local foodstuffs reflecting culturally enrooted consumption patterns. Camel milk and meat are esteemed in the regions of interest for their medicinal properties; camel meat is also frequently eaten on special occasions or for ritual celebrations (Jansen et al., 2016). It is, therefore, not unreasonable to assume that a proportion of illegal seizures of milk products and red meat originate from camels.
Significant knowledge gaps exist about prion disease in camels. Although PrPSc is believed to be the most useful marker of TSE disease identified to date, it has also been shown that its presence does not always directly correlate with infectious titres and that bioassay is still required for verification of infection (Chianini et al., 2015). So far, this has not been reported for CPD. The relative heat resistance of camel prions is also unknown, a factor which could affect the risk pathway if it were proven to show a greater susceptibility to heat than BSE or scrapie prions. Disease progression in CPD could also affect the risk pathway, specifically the prevalence of infection in camel products, if the slaughter age of most camels is young and disease is only detected in older animals. Likewise, products from animals with CPD but not yet showing clinical signs could also contribute to the probability of entry; this is particularly important regarding the long incubation period of the prion diseases. Further research to gain a better understanding into the CPD agent behaviour and improvement of the market traceability of camel products may alter the probability estimates stated here and should be considered in future risk assessments.
In conclusion, this paper assesses the annual probability of at least one entry event of camel products containing the CPD agent into the UK. The probability of entry from the Middle East or North Africa was considered to be highest from legal import of milk and cheese and the illegal import of camel meat, milk and cheese. These estimates are associated with high uncertainty due to the number of assumptions made throughout the risk pathway in particular the prevalence of CPD in camels, and of the CPD agent in camel products, and the number of products illegally entering the UK. However, this assessment does not consider the consequence of the exposure of uninfected animal populations to these products, only the probability of entry of the agent. Therefore, whilst a high probability of entry of the CPD agent has been estimated for some products, whether there is a subsequent probability of onward transmission is unknown (Fryer and McLean, 2011). The zoonotic potential of CPD is unknown but there is currently no evidence of zoonotic transmission of TSEs other than BSE to humans. Further research to look at the zoonotic potential and risks to public health would be beneficial.
Tables 3, 4, and 5 not shown here...tss
Ethics statement
The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to. No ethical approval was required as this is a risk assessment article with no original research data.’
Funding
“This work was funded by Defra, Scottish Government and Welsh Government through funding to the APHA Project ED1043 Enhancing surveillance, facilitating and improving outbreak response and informing policy” Declaration of Competing Interest
None.
References
Camel prion disease: a possible emerging disease in dromedary camel populations?
The identification of a new prion disease in dromedary camels in Algeria and Tunisia, called camel prion disease (CPD), extends the spectrum of animal species naturally susceptible to prion diseases and opens up new research areas for investigation.
Camel prion disease was identified in 2018 in adult camels showing clinical signs at the ante mortem inspection at slaughterhouses in the region of Ouargla (Algeria), and in 2019 in the region of Tataouine (Tunisia). It adds to the group of existing animal prion diseases, including scrapie in sheep and goats, chronic wasting disease (CWD) in cervids and BSE (mainly in bovines). The detection of a new prion disease in the dromedary population requires attention and investigation needs to be carried out to assess the risks of this disease to animal and public health. As of today, very limited epidemiological information is available to assess the prevalence, geographical distribution and dynamic of the transmission of the disease.
Based on the clinical signs suggesting prion disease, CPD seems to have occurred in 3.1% of the dromedaries brought to the abattoir in Ouargla. Pathognomonic neurodegeneration and diseasespecific prion protein (PrPSc) were detected in brain tissue from three symptomatic animals (source: CDC article wwwnc.cdc.gov/eid/article/24/6/17-2007_article).
In May 2019, the OIE received a report from Tunisia on a single case of a 12-year-old slaughtered dromedary camel showing neurological signs confirmed as CPD by the Istituto Superiore di Sanità (ISS) based in Italy.
©B. Babelhadj/University Kasdi Merbah, Algeria www.oiebulletin.com 2
Is camel prion disease transmissible in natural conditions?
The involvement of lymphoid tissue in prion replication, observed both in the Algeria and Tunisia cases, is suggestive of a peripheral pathogenesis, which is thought to be a prerequisite for prion shedding into the environment. As with other animal prion diseases, such as scrapie and CWD, in which lymphoid tissues are extensively involved and horizontal transmission occurs efficiently under natural conditions, the detection of prion proteins in lymph nodes is suggestive of the infectious nature of CPD and concurs to hypothesise the potential impact of CPD on animal health. No evidence is currently available with which to argue for the relevance of CPD for human health. However, no absolute species barrier exists in prion diseases and minimising the exposure of humans to prion-infected animal products is an essential aspect of public health protection. As for the relationship between CPD and other animal prion diseases, preliminary analyses suggest that CPD prions have a different molecular signature from scrapie and BSE.
Actions on the follow up of CPD
Since the first description of CPD, the OIE promoted discussions on the impact of this new disease through the OIE Scientific Commission for Animal Diseases (Scientific Commission). The Scientific Commission consulted two OIE ad hoc Groups, one on BSE risk status evaluation of Members and the other on camelids. It analysed the information available from the Algeria and Tunisia cases to evaluate if CPD should be considered an ‘emerging disease’ based on the criteria listed in the Terrestrial Animal Health Code1
. The OIE Scientific Commission noted that limited surveillance data were available on the prevalence of CPD and that the evidence was not sufficient to measure, at that time, the impact of the disease on animal or public health. Therefore, it was concluded that, with the current knowledge, CPD did not currently meet the criteria to be considered an emerging disease. Nonetheless, it was emphasised that CPD should be considered as a new disease not to be overlooked and called for the collection of further scientific evidence through research and surveillance in the affected countries and in countries with dromedary camel populations to measure the impact of the disease. As new scientific evidence becomes available,the OIE Scientific Commission will reassess whether this disease should be considered as an emerging disease.
The worldwide camel population is ~35 million head (FAO, 2019), 88% of which is found in Africa. The camel farming system is evolving rapidly, and these animals represent vital sources of meat, milk and transportation for millions of people living in the most arid regions of the world. This makes it necessary to assess the risk for animal and human health and to develop evidence-based policies to control and limit the spread of the disease in animals, and to minimise human exposure. As a first step, the awareness of Veterinary Services about CPD and its diagnostic capacity needs to be improved in all countries where dromedaries are part of the domestic livestock.
At the regional level, CPD was first discussed in the 18th Joint Permanent Committee of the Mediterranean Animal Health Network (REMESA) held in Cairo, Egypt, in June 2019 where an expert 1 a new occurrence in an animal of a disease, infection or infestation, causing a significant impact on animal or public health resulting from a) a change of a known pathogenic agent or its spread to a new geographic area or species, or b) a previously unrecognised pathogenic agent or disease diagnosed for the first time www.oiebulletin.com
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from ISS, Italy, shared the knowledge available on the new disease with the 15 REMESA Member Countries. The discussion highlighted the need to strengthen surveillance systems in order to collect epidemiological data to inform the risk assessments. The results of these risk assessments will support the implementation of evidence-based policies to manage the risks in both animals and humans.
CPD was recently discussed at the 15thConference of the OIE Regional Commission for the Middle East in November. During this conference, the CAMENET (Camel Middle East Network) launched a wideranging proposal for training, coordinated surveillance and research on CPD. In addition, the ERFAN (Enhancing Research forAfrica Network), a platform aimed at enhancing scientific cooperation between Africa and Italy, during its 2nd ERFAN meeting for North Africa, presented a project on CPD with the objective of increasing CPD coordinated surveillance in North Africa.
The OIE, through its Reference Laboratories for prion diseases, and by involving the above scientific initiatives, is keeping a close watch on the evolution of the disease to gather scientific evidence and to allow a proper and more thorough assessment of the risk associated with this novel disease.
◼ December 2019
THURSDAY, AUGUST 06, 2020
Scrapie Documented in Tunisia
Thursday, August 1, 2019
Camel prion disease detected in Tunisian camels Camel prion disease detected in Tunisian camels
A novel prion disease first reported in three dromedary camels in Algeria in 2018 has now been detected in dromedaries in Tunisia, the second country to be affected within a year, ProMED Mail, the online reporting system of the International Society for Infectious Diseases, reported yesterday.
The Tunisian detection and the latest information about the disease, called camel prion disease (CPD) and sometimes referred to as "mad camel disease", came from a presentation at the Mediterranean Animal Health Network meeting, held in Cairo on Jun 26 and 27. According to the meeting presentation, CPD is spreading rapidly in the Ouargla region of Algeria where the disease was first identified in older camels at a slaughterhouse.
The scientists who presented at the meeting also said preliminary results suggest that the CPD prion is different from scrapie and bovine spongiform encephalitis (BSE, or "mad cow disease").
A comment from the ProMED Mail moderator Arnon Shimshony, DVM, associate professor of veterinary medicine at Hebrew University of Jerusalem, notes that the area where CPD was first found in Algeria is about 174 miles from the Tunisian border.
In the initial report on the first detection in Algerian camels, published in April 2018 in Emerging Infectious Diseases, described disease-specific prion protein in brain tissues from symptomatic camels, including positive samples in lymph nodes, suggesting infection. The moderator also requested more details about the detections in Tunisia, including location, clinical signs, and ages and origins of affected camels. Jul 29 ProMED Mail post Apr 18, 2018, CIDRAP News story "'Mad camel' disease? New prion infection causes alarm"
***> NEW TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE (MAD CAMEL DISEASE) IN A NEW SPECIES <***
NEW OUTBREAK OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY TSE PRION DISEASE IN A NEW SPECIES
Subject: Prion Disease in Dromedary Camels, Algeria
Our identification of this prion disease in a geographically widespread livestock species requires urgent enforcement of surveillance and assessment of the potential risks to human and animal health.
Wednesday, May 30, 2018
Dromedary camels in northern Africa have a neurodegenerative prion disease that may have originated decades ago
***> IMPORTS AND EXPORTS <***
***> SEE MASSIVE AMOUNTS OF BANNED ANIMAL PROTEIN AKA MAD COW FEED IN COMMERCE USA DECADES AFTER POST BAN
Saturday, April 14, 2018
Dromedary Camels Algeria Prion (Mad Camel Disease) TSE BSE MRR Import Export Risk Factors Excluding Grains and Plants
Dromedary Camels Algeria Prion (Mad Camel Disease) TSE BSE MRR Import Export Risk Factors Excluding Grains and Plants
(Grains and Plants Materials Could Harbor the Transmissible Spongiform Encephalopathy TSE Prion agent...TSS)
Dromedary Camels Algeria Prion (Mad Camel Disease) TSE BSE MRR Import Export Risk Factors Excluding Grains and Plants
''Why is USDA "only" testing 25,000 samples a year?
TUESDAY, AUGUST 18, 2020
Sheep Scrapie, Bovine BSE, Cervid CWD, ZOONOSIS, TSE Prion Roundup August 18, 2020
MONDAY, AUGUST 24, 2020
Very low oral exposure to prions of brain or saliva origin can transmit chronic wasting disease
FRIDAY, AUGUST 7, 2020
National List of Reportable Animal Diseases (NLRAD) proposed rule CWD, Scrapie, BSE, TSE, Prion Disease Singeltary Submission Docket APHIS-2017-0002
THURSDAY, SEPTEMBER 10, 2020
Saskatchewan, Canada, Chronic Wasting Disease CWD TSE Prion
MONDAY, SEPTEMBER 14, 2020
Norway Chronic Wasting Disease (CWD) identified in a wild reindeer at Hardanger Plateau
SUNDAY, AUGUST 30, 2020
Texas CWD TSE Prion 3 More Documented, 185 Cases To Date
MONDAY, JULY 27, 2020
APHIS USDA Nor98-like scrapie was confirmed in a sheep sampled at slaughter in May 2020
MONDAY, JULY 27, 2020
Experimental study using multiple strains of prion disease in cattle reveals an inverse relationship between incubation time and misfolded prion accumulation, neuroinflammation and autophagy
WEDNESDAY, JUNE 10, 2020
Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice
CWD TSE Prion Zoonosis
> However, to date, no CWD infections have been reported in people.
this statement is starting to sound like a broken record.
when and who makes the final decision that cwd tse prion is zoonosis, and how much more science do you need?
> However, to date, no CWD infections have been reported in people.
key word here is ‘reported’. science has shown that CWD in humans will look like sporadic CJD. SO, how can one assume that CWD has not already transmitted to humans? they can’t, and it’s as simple as that. from all recorded science to date, CWD has already transmitted to humans, and it’s being misdiagnosed as sporadic CJD. …terry
*** LOOKING FOR CWD IN HUMANS AS nvCJD or as an ATYPICAL CJD, LOOKING IN ALL THE WRONG PLACES $$$ ***
*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***
Chronic Wasting Disease CWD TSE Prion aka mad deer disease zoonosis
We hypothesize that:
(1) The classic CWD prion strain can infect humans at low levels in the brain and peripheral lymphoid tissues;
(2) The cervid-to-human transmission barrier is dependent on the cervid prion strain and influenced by the host (human) prion protein (PrP) primary sequence;
(3) Reliable essays can be established to detect CWD infection in humans; and
(4) CWD transmission to humans has already occurred. We will test these hypotheses in 4 Aims using transgenic (Tg) mouse models and complementary in vitro approaches.
ZOONOTIC CHRONIC WASTING DISEASE CWD TSE PRION UPDATE
Prion 2017 Conference
First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress Stefanie Czub1, Walter Schulz-Schaeffer2, Christiane Stahl-Hennig3, Michael Beekes4, Hermann Schaetzl5 and Dirk Motzkus6 1
University of Calgary Faculty of Veterinary Medicine/Canadian Food Inspection Agency; 2Universitatsklinikum des Saarlandes und Medizinische Fakultat der Universitat des Saarlandes; 3 Deutsches Primaten Zentrum/Goettingen; 4 Robert-Koch-Institut Berlin; 5 University of Calgary Faculty of Veterinary Medicine; 6 presently: Boehringer Ingelheim Veterinary Research Center; previously: Deutsches Primaten Zentrum/Goettingen
This is a progress report of a project which started in 2009. 21 cynomolgus macaques were challenged with characterized CWD material from white-tailed deer (WTD) or elk by intracerebral (ic), oral, and skin exposure routes. Additional blood transfusion experiments are supposed to assess the CWD contamination risk of human blood product. Challenge materials originated from symptomatic cervids for ic, skin scarification and partially per oral routes (WTD brain). Challenge material for feeding of muscle derived from preclinical WTD and from preclinical macaques for blood transfusion experiments. We have confirmed that the CWD challenge material contained at least two different CWD agents (brain material) as well as CWD prions in muscle-associated nerves.
Here we present first data on a group of animals either challenged ic with steel wires or per orally and sacrificed with incubation times ranging from 4.5 to 6.9 years at postmortem. Three animals displayed signs of mild clinical disease, including anxiety, apathy, ataxia and/or tremor. In four animals wasting was observed, two of those had confirmed diabetes. All animals have variable signs of prion neuropathology in spinal cords and brains and by supersensitive IHC, reaction was detected in spinal cord segments of all animals. Protein misfolding cyclic amplification (PMCA), real-time quaking-induced conversion (RT-QuiC) and PET-blot assays to further substantiate these findings are on the way, as well as bioassays in bank voles and transgenic mice.
At present, a total of 10 animals are sacrificed and read-outs are ongoing. Preclinical incubation of the remaining macaques covers a range from 6.4 to 7.10 years. Based on the species barrier and an incubation time of > 5 years for BSE in macaques and about 10 years for scrapie in macaques, we expected an onset of clinical disease beyond 6 years post inoculation.
PRION 2017 DECIPHERING NEURODEGENERATIVE DISORDERS
PRION 2018 CONFERENCE
Oral transmission of CWD into Cynomolgus macaques: signs of atypical disease, prion conversion and infectivity in macaques and bio-assayed transgenic mice
Hermann M. Schatzl, Samia Hannaoui, Yo-Ching Cheng, Sabine Gilch (Calgary Prion Research Unit, University of Calgary, Calgary, Canada) Michael Beekes (RKI Berlin), Walter Schulz-Schaeffer (University of Homburg/Saar, Germany), Christiane Stahl-Hennig (German Primate Center) & Stefanie Czub (CFIA Lethbridge).
To date, BSE is the only example of interspecies transmission of an animal prion disease into humans. The potential zoonotic transmission of CWD is an alarming issue and was addressed by many groups using a variety of in vitro and in vivo experimental systems. Evidence from these studies indicated a substantial, if not absolute, species barrier, aligning with the absence of epidemiological evidence suggesting transmission into humans. Studies in non-human primates were not conclusive so far, with oral transmission into new-world monkeys and no transmission into old-world monkeys. Our consortium has challenged 18 Cynomolgus macaques with characterized CWD material, focusing on oral transmission with muscle tissue. Some macaques have orally received a total of 5 kg of muscle material over a period of 2 years.
After 5-7 years of incubation time some animals showed clinical symptoms indicative of prion disease, and prion neuropathology and PrPSc deposition were detected in spinal cord and brain of some euthanized animals. PrPSc in immunoblot was weakly detected in some spinal cord materials and various tissues tested positive in RT-QuIC, including lymph node and spleen homogenates. To prove prion infectivity in the macaque tissues, we have intracerebrally inoculated 2 lines of transgenic mice, expressing either elk or human PrP. At least 3 TgElk mice, receiving tissues from 2 different macaques, showed clinical signs of a progressive prion disease and brains were positive in immunoblot and RT-QuIC. Tissues (brain, spinal cord and spleen) from these and pre-clinical mice are currently tested using various read-outs and by second passage in mice. Transgenic mice expressing human PrP were so far negative for clear clinical prion disease (some mice >300 days p.i.). In parallel, the same macaque materials are inoculated into bank voles.
Taken together, there is strong evidence of transmissibility of CWD orally into macaques and from macaque tissues into transgenic mouse models, although with an incomplete attack rate.
The clinical and pathological presentation in macaques was mostly atypical, with a strong emphasis on spinal cord pathology.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
Our ongoing studies will show whether the transmission of CWD into macaques and passage in transgenic mice represents a form of non-adaptive prion amplification, and whether macaque-adapted prions have the potential to infect mice expressing human PrP.
The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD..
***> The notion that CWD can be transmitted orally into both new-world and old-world non-human primates asks for a careful reevaluation of the zoonotic risk of CWD. <***
READING OVER THE PRION 2018 ABSTRACT BOOK, LOOKS LIKE THEY FOUND THAT from this study ;
P190 Human prion disease mortality rates by occurrence of chronic wasting disease in freeranging cervids, United States
Abrams JY (1), Maddox RA (1), Schonberger LB (1), Person MK (1), Appleby BS (2), Belay ED (1) (1) Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, GA, USA (2) Case Western Reserve University, National Prion Disease Pathology Surveillance Center (NPDPSC), Cleveland, OH, USA..
SEEMS THAT THEY FOUND Highly endemic states had a higher rate of prion disease mortality compared to non-CWD
states.
states.
AND ANOTHER STUDY;
P172 Peripheral Neuropathy in Patients with Prion Disease
Wang H(1), Cohen M(1), Appleby BS(1,2) (1) University Hospitals Cleveland Medical Center, Cleveland, Ohio (2) National Prion Disease Pathology Surveillance Center, Cleveland, Ohio..
IN THIS STUDY, THERE WERE autopsy-proven prion cases from the National Prion Disease Pathology Surveillance Center that were diagnosed between September 2016 to March 2017,
AND
included 104 patients. SEEMS THEY FOUND THAT The most common sCJD subtype was MV1-2 (30%), followed by MM1-2 (20%),
AND
THAT The Majority of cases were male (60%), AND half of them had exposure to wild game.
snip…
see more on Prion 2017 Macaque study from Prion 2017 Conference and other updated science on cwd tse prion zoonosis below…terry
PRION 2019 ABSTRACTS
1. Interspecies transmission of the chronic wasting disease agent
Justin Greenlee
Virus and Prion Research Unit, National Animal Disease Center, USDA Agriculture Research Service
ABSTRACT
The presentation will summarize the results of various studies conducted at our research center that assess the transmissibility of the chronic wasting disease (CWD) agent to cattle, pigs, raccoons, goats, and sheep. This will include specifics of the relative attack rates, clinical signs, and microscopic lesions with emphasis on how to differentiate cross-species transmission of the CWD agent from the prion diseases that naturally occur in hosts such as cattle or sheep. Briefly, the relative difficulty of transmitting the CWD agent to sheep and goats will be contrasted with the relative ease of transmitting the scrapie agent to white-tailed deer.
53. Evaluation of the inter-species transmission potential of different CWD isolates
Rodrigo Moralesa, Carlos Kramma,b, Paulina Sotoa, Adam Lyona, Sandra Pritzkowa, Claudio Sotoa
aMitchell Center for Alzheimer’s disease and Related Brain Disorders, Dept. of Neurology, McGovern School of Medicine University of Texas Health Science Center at Houston, TX, USA; bFacultad de Medicina, Universidad de los Andes, Santiago, Chile
ABSTRACT
Chronic Wasting Disease (CWD) has reached epidemic proportions in North America and has been identified in South Korea and Northern Europe. CWD-susceptible cervid species are known to share habitats with humans and other animals entering the human food chain. At present, the potential of CWD to infect humans and other animal species is not completely clear. The exploration of this issue acquires further complexity considering the differences in the prion protein sequence due to species-specific variations and polymorphic changes within species. While several species of cervids are naturally affected by CWD, white-tailed deer (WTD) is perhaps the most relevant due to its extensive use in hunting and as a source of food. Evaluation of inter-species prion infections using animals or mouse models is costly and time consuming. We and others have shown that the Protein Misfolding Cyclic Amplification (PMCA) technology reproduces, in an accelerated and inexpensive manner, the inter-species transmission of prions while preserving the strain features of the input PrPSc. In this work, we tested the potential of different WTD-derived CWD isolates to transmit to humans and other animal species relevant for human consumption using PMCA. For these experiments, CWD isolates homozygous for the most common WTD-PrP polymorphic changes (G96S) were used (96SS variant obtained from a pre-symptomatic prion infected WTD). Briefly, 96GG and 96SS CWD prions were adapted in homologous or heterologous substrate by PMCA through several (15) rounds. End products, as well as intermediates across the process, were tested for their inter-species transmission potentials. A similar process was followed to assess seed-templated misfolding of ovine, porcine, and bovine PrPC. Our results show differences on the inter-species transmission potentials of the four adapted materials generated (PrPC/PrPSc polymorphic combinations), being the homologous combinations of seed/substrate the ones with the greater apparent zoonotic potential. Surprisingly, 96SS prions adapted in homologous substrate were the ones showing the easiest potential to template PrPC misfolding from other animal species. In summary, our results show that a plethora of different CWD isolates, each comprising different potentials for inter-species transmission, may exist in the environment. These experiments may help to clarify an uncertain and potentially worrisome public health issue. Additional research in this area may be useful to advise on the design of regulations intended to stop the spread of CWD and predict unwanted zoonotic events.
56. Understanding chronic wasting disease spread potential for at-risk species
Catherine I. Cullingham, Anh Dao, Debbie McKenzie and David W. Coltman
Department of Biological Sciences, University of Alberta, Edmonton AB, Canada
CONTACT Catherine I. Cullingham cathy.cullingham@ualberta.ca
ABSTRACT
Genetic variation can be linked to susceptibility or resistance to a disease, and this information can help to better understand spread-risk in a population. Wildlife disease incidence is increasing, and this is resulting in negative impacts on the economy, biodiversity, and in some instances, human health. If we can find genetic variation that helps to inform which individuals are susceptible, then we can use this information on at-risk populations to better manage negative consequences. Chronic wasting disease, a fatal, transmissible spongiform encephalopathy of cervids (both wild and captive), continues to spread geographically, which has resulted in an increasing host-range. The disease agent (PrPCWD) is a misfolded conformer of native cellular protein (PrPC). In Canada, the disease is endemic in Alberta and Saskatchewan, infecting primarily mule deer and white-tail deer, with a smaller impact on elk and moose populations. As the extent of the endemic area continues to expand, additional species will be exposed to this disease, including bison, bighorn sheep, mountain goat, and pronghorn antelope. To better understand the potential spread-risk among these species, we reviewed the current literature on species that have been orally exposed to CWD to identify susceptible and resistant species. We then compared the amino acid polymorphisms of PrPC among these species to determine whether any sites were linked to susceptibility or resistance to CWD infection. We sequenced the entire PrP coding region in 578 individuals across at-risk populations to evaluate their potential susceptibility. Three amino acid sites (97, 170, and 174; human numbering) were significantly associated with susceptibility, but these were not fully discriminating. All but one species among the resistant group shared the same haplotype, and the same for the susceptible species. For the at-risk species, bison had the resistant haplotype, while bighorn sheep and mountain goats were closely associated with the resistant type. Pronghorn antelope and a newly identified haplotype in moose differed from the susceptible haplotype, but were still closely associated with it. These data suggest pronghorn antelope will be susceptible to CWD while bison are likely to be resistant. Based on this data, recommendations can be made regarding species to be monitored for possible CWD infection.
KEYWORDS: Chronic wasting disease; Prnp; wildlife disease; population genetics; ungulates
Thursday, May 23, 2019
Prion 2019 Emerging Concepts CWD, BSE, SCRAPIE, CJD, SCIENTIFIC PROGRAM Schedule and Abstracts
see full Prion 2019 Conference Abstracts
TUESDAY, NOVEMBER 04, 2014
Six-year follow-up of a point-source exposure to CWD contaminated venison in an Upstate New York community: risk behaviours and health outcomes 2005–2011
Authors, though, acknowledged the study was limited in geography and sample size and so it couldn't draw a conclusion about the risk to humans. They recommended more study. Dr. Ermias Belay was the report's principal author but he said New York and Oneida County officials are following the proper course by not launching a study. "There's really nothing to monitor presently. No one's sick," Belay said, noting the disease's incubation period in deer and elk is measured in years. "
FRIDAY, JULY 26, 2019
Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species
THURSDAY, OCTOBER 04, 2018
Cervid to human prion transmission 5R01NS088604-04 Update
snip…full text;
SATURDAY, FEBRUARY 09, 2019
Experts: Yes, chronic wasting disease in deer is a public health issue — for people
SATURDAY, FEBRUARY 23, 2019
Chronic Wasting Disease CWD TSE Prion and THE FEAST 2003 CDC an updated review of the science 2019
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).
Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
==============
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Juan Maria Torres a, Olivier Andreoletti b, J uan-Carlos Espinosa a. Vincent Beringue c. Patricia Aguilar a,
Natalia Fernandez-Borges a. and Alba Marin-Moreno a
"Centro de Investigacion en Sanidad Animal ( CISA-INIA ). Valdeolmos, Madrid. Spain; b UMR INRA -ENVT 1225 Interactions Holes Agents Pathogenes. ENVT. Toulouse. France: "UR892. Virologie lmmunologie MolécuIaires, Jouy-en-Josas. France
Dietary exposure to bovine spongiform encephalopathy (BSE) contaminated bovine tissues is considered as the origin of variant Creutzfeldt Jakob (vCJD) disease in human. To date, BSE agent is the only recognized zoonotic prion... Despite the variety of Transmissible Spongiform Encephalopathy (TSE) agents that have been circulating for centuries in farmed ruminants there is no apparent epidemiological link between exposure to ruminant products and the occurrence of other form of TSE in human like sporadic Creutzfeldt Jakob Disease (sCJD). However, the zoonotic potential of the diversity of circulating TSE agents has never been systematically assessed. The major issue in experimental assessment of TSEs zoonotic potential lies in the modeling of the ‘species barrier‘, the biological phenomenon that limits TSE agents’ propagation from a species to another. In the last decade, mice genetically engineered to express normal forms of the human prion protein has proved essential in studying human prions pathogenesis and modeling the capacity of TSEs to cross the human species barrier.
To assess the zoonotic potential of prions circulating in farmed ruminants, we study their transmission ability in transgenic mice expressing human PrPC (HuPrP-Tg). Two lines of mice expressing different forms of the human PrPC (129Met or 129Val) are used to determine the role of the Met129Val dimorphism in susceptibility/resistance to the different agents.
These transmission experiments confirm the ability of BSE prions to propagate in 129M- HuPrP-Tg mice and demonstrate that Met129 homozygotes may be susceptible to BSE in sheep or goat to a greater degree than the BSE agent in cattle and that these agents can convey molecular properties and neuropathological indistinguishable from vCJD. However homozygous 129V mice are resistant to all tested BSE derived prions independently of the originating species suggesting a higher transmission barrier for 129V-PrP variant.
Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
***> why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man.
***> I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough.
***> Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.
snip...
R. BRADLEY
Title: Transmission of scrapie prions to primate after an extended silent incubation period)
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
***> Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility. <***
Transmission of scrapie prions to primate after an extended silent incubation period
Emmanuel E. Comoy, Jacqueline Mikol, Sophie Luccantoni-Freire, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Valérie Durand, Capucine Dehen, Olivier Andreoletti, Cristina Casalone, Juergen A. Richt, Justin J. Greenlee, Thierry Baron, Sylvie L. Benestad, Paul Brown & Jean-Philippe Deslys Scientific Reports volume 5, Article number: 11573 (2015) | Download Citation
Abstract
Classical bovine spongiform encephalopathy (c-BSE) is the only animal prion disease reputed to be zoonotic, causing variant Creutzfeldt-Jakob disease (vCJD) in humans and having guided protective measures for animal and human health against animal prion diseases. Recently, partial transmissions to humanized mice showed that the zoonotic potential of scrapie might be similar to c-BSE. We here report the direct transmission of a natural classical scrapie isolate to cynomolgus macaque, a highly relevant model for human prion diseases, after a 10-year silent incubation period, with features similar to those reported for human cases of sporadic CJD. Scrapie is thus actually transmissible to primates with incubation periods compatible with their life expectancy, although fourfold longer than BSE. Long-term experimental transmission studies are necessary to better assess the zoonotic potential of other prion diseases with high prevalence, notably Chronic Wasting Disease of deer and elk and atypical/Nor98 scrapie.
SNIP...
Discussion We describe the transmission of spongiform encephalopathy in a non-human primate inoculated 10 years earlier with a strain of sheep c-scrapie. Because of this extended incubation period in a facility in which other prion diseases are under study, we are obliged to consider two alternative possibilities that might explain its occurrence. We first considered the possibility of a sporadic origin (like CJD in humans). Such an event is extremely improbable because the inoculated animal was 14 years old when the clinical signs appeared, i.e. about 40% through the expected natural lifetime of this species, compared to a peak age incidence of 60–65 years in human sporadic CJD, or about 80% through their expected lifetimes. Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.
The second possibility is a laboratory cross-contamination. Three facts make this possibility equally unlikely. First, handling of specimens in our laboratory is performed with fastidious attention to the avoidance of any such cross-contamination. Second, no laboratory cross-contamination has ever been documented in other primate laboratories, including the NIH, even between infected and uninfected animals housed in the same or adjacent cages with daily intimate contact (P. Brown, personal communication). Third, the cerebral lesion profile is different from all the other prion diseases we have studied in this model19, with a correlation between cerebellar lesions (massive spongiform change of Purkinje cells, intense PrPres staining and reactive gliosis26) and ataxia. The iron deposits present in the globus pallidus are a non specific finding that have been reported previously in neurodegenerative diseases and aging27. Conversely, the thalamic lesion was reminiscent of a metabolic disease due to thiamine deficiency28 but blood thiamine levels were within normal limits (data not shown). The preferential distribution of spongiform change in cortex associated with a limited distribution in the brainstem is reminiscent of the lesion profile in MM2c and VV1 sCJD patients29, but interspecies comparison of lesion profiles should be interpreted with caution. It is of note that the same classical scrapie isolate induced TSE in C57Bl/6 mice with similar incubation periods and lesional profiles as a sample derived from a MM1 sCJD patient30.
We are therefore confident that the illness in this cynomolgus macaque represents a true transmission of a sheep c-scrapie isolate directly to an old-world monkey, which taxonomically resides in the primate subdivision (parvorder of catarrhini) that includes humans. With an homology of its PrP protein with humans of 96.4%31, cynomolgus macaque constitutes a highly relevant model for assessing zoonotic risk of prion diseases. Since our initial aim was to show the absence of transmission of scrapie to macaques in the worst-case scenario, we obtained materials from a flock of naturally-infected sheep, affecting animals with different genotypes32. This c-scrapie isolate exhibited complete transmission in ARQ/ARQ sheep (332 ± 56 days) and Tg338 transgenic mice expressing ovine VRQ/VRQ prion protein (220 ± 5 days) (O. Andreoletti, personal communication). From the standpoint of zoonotic risk, it is important to note that sheep with c-scrapie (including the isolate used in our study) have demonstrable infectivity throughout their lymphoreticular system early in the incubation period of the disease (3 months-old for all the lymphoid organs, and as early as 2 months-old in gut-associated lymph nodes)33. In addition, scrapie infectivity has been identified in blood34, milk35 and skeletal muscle36 from asymptomatic but scrapie infected small ruminants which implies a potential dietary exposure for consumers.
Two earlier studies have reported the occurrence of clinical TSE in cynomolgus macaques after exposures to scrapie isolates. In the first study, the “Compton” scrapie isolate (derived from an English sheep) and serially propagated for 9 passages in goats did not transmit TSE in cynomolgus macaque, rhesus macaque or chimpanzee within 7 years following intracerebral challenge1; conversely, after 8 supplementary passages in conventional mice, this “Compton” isolate induced TSE in a cynomolgus macaque 5 years after intracerebral challenge, but rhesus macaques and chimpanzee remained asymptomatic 8.5 years post-exposure8. However, multiple successive passages that are classically used to select laboratory-adapted prion strains can significantly modify the initial properties of a scrapie isolate, thus questioning the relevance of zoonotic potential for the initial sheep-derived isolate. The same isolate had also induced disease into squirrel monkeys (new-world monkey)9. A second historical observation reported that a cynomolgus macaque developed TSE 6 years post-inoculation with brain homogenate from a scrapie-infected Suffolk ewe (derived from USA), whereas a rhesus macaque and a chimpanzee exposed to the same inoculum remained healthy 9 years post-exposure1. This inoculum also induced TSE in squirrel monkeys after 4 passages in mice. Other scrapie transmission attempts in macaque failed but had more shorter periods of observation in comparison to the current study. Further, it is possible that there are differences in the zoonotic potential of different scrapie strains.
The most striking observation in our study is the extended incubation period of scrapie in the macaque model, which has several implications. Firstly, our observations constitute experimental evidence in favor of the zoonotic potential of c-scrapie, at least for this isolate that has been extensively studied32,33,34,35,36. The cross-species zoonotic ability of this isolate should be confirmed by performing duplicate intracerebral exposures and assessing the transmissibility by the oral route (a successful transmission of prion strains through the intracerebral route may not necessarily indicate the potential for oral transmission37). However, such confirmatory experiments may require more than one decade, which is hardly compatible with current general management and support of scientific projects; thus this study should be rather considered as a case report.
Secondly, transmission of c-BSE to primates occurred within 8 years post exposure for the lowest doses able to transmit the disease (the survival period after inoculation is inversely proportional to the initial amount of infectious inoculum). The occurrence of scrapie 10 years after exposure to a high dose (25 mg) of scrapie-infected sheep brain suggests that the macaque has a higher species barrier for sheep c-scrapie than c-BSE, although it is notable that previous studies based on in vitro conversion of PrP suggested that BSE and scrapie prions would have a similar conversion potential for human PrP38.
Thirdly, prion diseases typically have longer incubation periods after oral exposure than after intracerebral inoculations: since humans can develop Kuru 47 years after oral exposure39, an incubation time of several decades after oral exposure to scrapie would therefore be expected, leading the disease to occur in older adults, i.e. the peak age for cases considered to be sporadic disease, and making a distinction between scrapie-associated and truly sporadic disease extremely difficult to appreciate.
Fourthly, epidemiologic evidence is necessary to confirm the zoonotic potential of an animal disease suggested by experimental studies. A relatively short incubation period and a peculiar epidemiological situation (e.g., all the first vCJD cases occurring in the country with the most important ongoing c-BSE epizootic) led to a high degree of suspicion that c-BSE was the cause of vCJD. Sporadic CJD are considered spontaneous diseases with an almost stable and constant worldwide prevalence (0.5–2 cases per million inhabitants per year), and previous epidemiological studies were unable to draw a link between sCJD and classical scrapie6,7,40,41, even though external causes were hypothesized to explain the occurrence of some sCJD clusters42,43,44. However, extended incubation periods exceeding several decades would impair the predictive values of epidemiological surveillance for prion diseases, already weakened by a limited prevalence of prion diseases and the multiplicity of isolates gathered under the phenotypes of “scrapie” and “sporadic CJD”.
Fifthly, considering this 10 year-long incubation period, together with both laboratory and epidemiological evidence of decade or longer intervals between infection and clinical onset of disease, no premature conclusions should be drawn from negative transmission studies in cynomolgus macaques with less than a decade of observation, as in the aforementioned historical transmission studies of scrapie to primates1,8,9. Our observations and those of others45,46 to date are unable to provide definitive evidence regarding the zoonotic potential of CWD, atypical/Nor98 scrapie or H-type BSE. The extended incubation period of the scrapie-affected macaque in the current study also underscores the limitations of rodent models expressing human PrP for assessing the zoonotic potential of some prion diseases since their lifespan remains limited to approximately two years21,47,48. This point is illustrated by the fact that the recently reported transmission of scrapie to humanized mice was not associated with clinical signs for up to 750 days and occurred in an extreme minority of mice with only a marginal increase in attack rate upon second passage13. The low attack rate in these studies is certainly linked to the limited lifespan of mice compared to the very long periods of observation necessary to demonstrate the development of scrapie. Alternatively, one could estimate that a successful second passage is the result of strain adaptation to the species barrier, thus poorly relevant of the real zoonotic potential of the original scrapie isolate of sheep origin49. The development of scrapie in this primate after an incubation period compatible with its lifespan complements the study conducted in transgenic (humanized) mice; taken together these studies suggest that some isolates of sheep scrapie can promote misfolding of the human prion protein and that scrapie can develop within the lifespan of some primate species.
In addition to previous studies on scrapie transmission to primate1,8,9 and the recently published study on transgenic humanized mice13, our results constitute new evidence for recommending that the potential risk of scrapie for human health should not be dismissed. Indeed, human PrP transgenic mice and primates are the most relevant models for investigating the human transmission barrier. To what extent such models are informative for measuring the zoonotic potential of an animal TSE under field exposure conditions is unknown. During the past decades, many protective measures have been successfully implemented to protect cattle from the spread of c-BSE, and some of these measures have been extended to sheep and goats to protect from scrapie according to the principle of precaution. Since cases of c-BSE have greatly reduced in number, those protective measures are currently being challenged and relaxed in the absence of other known zoonotic animal prion disease. We recommend that risk managers should be aware of the long term potential risk to human health of at least certain scrapie isolates, notably for lymphotropic strains like the classical scrapie strain used in the current study. Relatively high amounts of infectivity in peripheral lymphoid organs in animals infected with these strains could lead to contamination of food products produced for human consumption. Efforts should also be maintained to further assess the zoonotic potential of other animal prion strains in long-term studies, notably lymphotropic strains with high prevalence like CWD, which is spreading across North America, and atypical/Nor98 scrapie (Nor98)50 that was first detected in the past two decades and now represents approximately half of all reported cases of prion diseases in small ruminants worldwide, including territories previously considered as scrapie free... Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
America BSE 589.2001 FEED REGULATIONS, BSE SURVEILLANCE, BSE TESTING, and CJD TSE Prion
***> cattle, pigs, sheep, cwd, tse, prion, oh my!
***> In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006).
Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008). In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008), however the risk appetite for a public health threat may still find this level unacceptable.
cwd scrapie pigs oral routes
***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***
>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***
***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%).
***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
snip.....
In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law. Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES.
It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
snip.....
36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison. snip..... The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip.....
In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion. snip..... In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible... For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.
snip.....
Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.
snip.....
***> READ THIS VERY, VERY, CAREFULLY, AUGUST 1997 MAD COW FEED BAN WAS A SHAM, AS I HAVE STATED SINCE 1997! 3 FAILSAFES THE FDA ET AL PREACHED AS IF IT WERE THE GOSPEL, IN TERMS OF MAD COW BSE DISEASE IN USA, AND WHY IT IS/WAS/NOT A PROBLEM FOR THE USA, and those are;
BSE TESTING (failed terribly and proven to be a sham)
BSE SURVEILLANCE (failed terribly and proven to be a sham)
BSE 589.2001 FEED REGULATIONS (another colossal failure, and proven to be a sham)
these are facts folks. trump et al just admitted it with the feed ban.
see;
FDA Reports on VFD Compliance
John Maday
August 30, 2019 09:46 AM VFD-Form 007 (640x427)
Before and after the current Veterinary Feed Directive rules took full effect in January, 2017, the FDA focused primarily on education and outreach. ( John Maday ) Before and after the current Veterinary Feed Directive (VFD) rules took full effect in January, 2017, the FDA focused primarily on education and outreach to help feed mills, veterinarians and producers understand and comply with the requirements. Since then, FDA has gradually increased the number of VFD inspections and initiated enforcement actions when necessary. On August 29, FDA released its first report on inspection and compliance activities. The report, titled “Summary Assessment of Veterinary Feed Directive Compliance Activities Conducted in Fiscal Years 2016 – 2018,” is available online.
SUNDAY, SEPTEMBER 1, 2019
***> FDA Reports on VFD Compliance
***> cattle, pigs, sheep, cwd, tse, prion, oh my!
***> In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006).
Sheep and cattle may be exposed to CWD via common grazing areas with affected deer but so far, appear to be poorly susceptible to mule deer CWD (Sigurdson, 2008). In contrast, cattle are highly susceptible to white-tailed deer CWD and mule deer CWD in experimental conditions but no natural CWD infections in cattle have been reported (Sigurdson, 2008; Hamir et al., 2006). It is not known how susceptible humans are to CWD but given that the prion can be present in muscle, it is likely that humans have been exposed to the agent via consumption of venison (Sigurdson, 2008). Initial experimental research suggests that human susceptibility to CWD is low and there may be a robust species barrier for CWD transmission to humans (Sigurdson, 2008), however the risk appetite for a public health threat may still find this level unacceptable.
cwd scrapie pigs oral routes
***> However, at 51 months of incubation or greater, 5 animals were positive by one or more diagnostic methods. Furthermore, positive bioassay results were obtained from all inoculated groups (oral and intracranial; market weight and end of study) suggesting that swine are potential hosts for the agent of scrapie. <***
>*** Although the current U.S. feed ban is based on keeping tissues from TSE infected cattle from contaminating animal feed, swine rations in the U.S. could contain animal derived components including materials from scrapie infected sheep and goats. These results indicating the susceptibility of pigs to sheep scrapie, coupled with the limitations of the current feed ban, indicates that a revision of the feed ban may be necessary to protect swine production and potentially human health. <***
***> Results: PrPSc was not detected by EIA and IHC in any RPLNs. All tonsils and MLNs were negative by IHC, though the MLN from one pig in the oral <6 month group was positive by EIA. PrPSc was detected by QuIC in at least one of the lymphoid tissues examined in 5/6 pigs in the intracranial <6 months group, 6/7 intracranial >6 months group, 5/6 pigs in the oral <6 months group, and 4/6 oral >6 months group. Overall, the MLN was positive in 14/19 (74%) of samples examined, the RPLN in 8/18 (44%), and the tonsil in 10/25 (40%).
***> Conclusions: This study demonstrates that PrPSc accumulates in lymphoid tissues from pigs challenged intracranially or orally with the CWD agent, and can be detected as early as 4 months after challenge. CWD-infected pigs rarely develop clinical disease and if they do, they do so after a long incubation period. This raises the possibility that CWD-infected pigs could shed prions into their environment long before they develop clinical disease. Furthermore, lymphoid tissues from CWD-infected pigs could present a potential source of CWD infectivity in the animal and human food chains.
Friday, December 14, 2012
DEFRA U.K. What is the risk of Chronic Wasting Disease CWD being introduced into Great Britain? A Qualitative Risk Assessment October 2012
snip.....
In the USA, under the Food and Drug Administration's BSE Feed Regulation (21 CFR 589.2000) most material (exceptions include milk, tallow, and gelatin) from deer and elk is prohibited for use in feed for ruminant animals. With regards to feed for non-ruminant animals, under FDA law, CWD positive deer may not be used for any animal feed or feed ingredients. For elk and deer considered at high risk for CWD, the FDA recommends that these animals do not enter the animal feed system. However, this recommendation is guidance and not a requirement by law. Animals considered at high risk for CWD include:
1) animals from areas declared to be endemic for CWD and/or to be CWD eradication zones and
2) deer and elk that at some time during the 60-month period prior to slaughter were in a captive herd that contained a CWD-positive animal.
Therefore, in the USA, materials from cervids other than CWD positive animals may be used in animal feed and feed ingredients for non-ruminants.
The amount of animal PAP that is of deer and/or elk origin imported from the USA to GB can not be determined, however, as it is not specified in TRACES.
It may constitute a small percentage of the 8412 kilos of non-fish origin processed animal proteins that were imported from US into GB in 2011.
Overall, therefore, it is considered there is a __greater than negligible risk___ that (nonruminant) animal feed and pet food containing deer and/or elk protein is imported into GB.
There is uncertainty associated with this estimate given the lack of data on the amount of deer and/or elk protein possibly being imported in these products.
snip.....
36% in 2007 (Almberg et al., 2011). In such areas, population declines of deer of up to 30 to 50% have been observed (Almberg et al., 2011). In areas of Colorado, the prevalence can be as high as 30% (EFSA, 2011). The clinical signs of CWD in affected adults are weight loss and behavioural changes that can span weeks or months (Williams, 2005). In addition, signs might include excessive salivation, behavioural alterations including a fixed stare and changes in interaction with other animals in the herd, and an altered stance (Williams, 2005). These signs are indistinguishable from cervids experimentally infected with bovine spongiform encephalopathy (BSE). Given this, if CWD was to be introduced into countries with BSE such as GB, for example, infected deer populations would need to be tested to differentiate if they were infected with CWD or BSE to minimise the risk of BSE entering the human food-chain via affected venison. snip..... The rate of transmission of CWD has been reported to be as high as 30% and can approach 100% among captive animals in endemic areas (Safar et al., 2008).
snip.....
In summary, in endemic areas, there is a medium probability that the soil and surrounding environment is contaminated with CWD prions and in a bioavailable form. In rural areas where CWD has not been reported and deer are present, there is a greater than negligible risk the soil is contaminated with CWD prion. snip..... In summary, given the volume of tourists, hunters and servicemen moving between GB and North America, the probability of at least one person travelling to/from a CWD affected area and, in doing so, contaminating their clothing, footwear and/or equipment prior to arriving in GB is greater than negligible... For deer hunters, specifically, the risk is likely to be greater given the increased contact with deer and their environment. However, there is significant uncertainty associated with these estimates.
snip.....
Therefore, it is considered that farmed and park deer may have a higher probability of exposure to CWD transferred to the environment than wild deer given the restricted habitat range and higher frequency of contact with tourists and returning GB residents.
snip.....
TUESDAY, OCTOBER 29, 2019
America BSE 589.2001 FEED REGULATIONS, BSE SURVEILLANCE, BSE TESTING, and CJD TSE Prion
FRIDAY, NOVEMBER 08, 2019
EFSA Panel on Biological Hazards (BIOHAZ) Update on chronic wasting disease (CWD) III
MONDAY, FEBRUARY 25, 2019
***> MAD DOGS AND ENGLISHMEN BSE, SCRAPIE, CWD, CJD, TSE PRION A REVIEW 2019
MONDAY, JULY 27, 2020
BSE Inquiry DFA's a review
THURSDAY, JULY 02, 2020
Variant Creutzfeldt–Jakob Disease Diagnosed 7.5 Years after Occupational Exposure
Volume 26, Number 8—August 2020
Sporadic Creutzfeldt-Jakob Disease among Physicians, Germany, 1993–2018 high proportion of physicians with sCJD were surgeons
DEEP THROAT TO TSS 2000-2001 (take these old snips of emails with how ever many grains of salt you wish. ...tss)
The most frightening thing I have read all day is the report of Gambetti's finding of a new strain of sporadic cjd in young people...Dear God, what in the name of all that is holy is that!!! If the US has different strains of scrapie.....why???? than the UK...then would the same mechanisms that make different strains of scrapie here make different strains of BSE...if the patterns are different in sheep and mice for scrapie.....could not the BSE be different in the cattle, in the mink, in the humans.......
I really think the slides or tissues and everything from these young people with the new strain of sporadic cjd should be put up to be analyzed by many, many experts in cjd........bse.....scrapie Scrape the damn slide and put it into mice.....wait.....chop up the mouse brain and and spinal cord........put into some more mice.....dammit amplify the thing and start the damned research.....This is NOT rocket science...we need to use what we know and get off our butts and move....the whining about how long everything takes.....well it takes a whole lot longer if you whine for a year and then start the research!!!
Not sure where I read this but it was a recent press release or something like that: I thought I would fall out of my chair when I read about how there was no worry about infectivity from a histopath slide or tissues because they are preserved in formic acid, or formalin or formaldehyde.....for God's sake........ Ask any pathologist in the UK what the brain tissues in the formalin looks like after a year.......it is a big fat sponge...the agent continues to eat the brain ......you can't make slides anymore because the agent has never stopped........and the old slides that are stained with Hemolysin and Eosin......they get holier and holier and degenerate and continue...what you looked at 6 months ago is not there........Gambetti better be photographing every damned thing he is looking at.....
Okay, you need to know. You don't need to pass it on as nothing will come of it and there is not a damned thing anyone can do about it. Don't even hint at it as it will be denied and laughed at.......... USDA is gonna do as little as possible until there is actually a human case in the USA of the nvcjd........if you want to move this thing along and shake the earth....then we gotta get the victims families to make sure whoever is doing the autopsy is credible, trustworthy, and a saint with the courage of Joan of Arc........I am not kidding!!!! so, unless we get a human death from EXACTLY the same form with EXACTLY the same histopath lesions as seen in the UK nvcjd........forget any action........it is ALL gonna be sporadic!!!
And, if there is a case.......there is gonna be every effort to link it to international travel, international food, etc. etc. etc. etc. etc. They will go so far as to find out if a sex partner had ever traveled to the UK/europe, etc. etc. .... It is gonna be a long, lonely, dangerous twisted journey to the truth. They have all the cards, all the money, and are willing to threaten and carry out those threats....and this may be their biggest downfall...
Thanks as always for your help. Recently had a very startling revelation from a rather senior person in government here..........knocked me out of my chair........you must keep pushing. If I was a power person....I would be demanding that there be a least a million bovine tested as soon as possible and aggressively seeking this disease. The big players are coming out of the woodwork as there is money to be made!!! In short: "FIRE AT WILL"!!! for the very dumb....who's "will"! "Will be the burden to bare if there is any coverup!"
again it was said years ago and it should be taken seriously....BSE will NEVER be found in the US! As for the BSE conference call...I think you did a great service to freedom of information and making some people feign integrity...I find it scary to see that most of the "experts" are employed by the federal government or are supported on the "teat" of federal funds. A scary picture! I hope there is a confidential panel organized by the new government to really investigate this thing.
USA EMERGENCY 50 STATE BSE CONFERENCE CALL
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
2 January 2000 British Medical Journal U.S.
Scientist should be concerned with a CJD epidemic in the U.S., as well
15 November 1999 British Medical Journal hvCJD in the USA * BSE in U.S.
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.
doi:10.1016/S1473-3099(03)00715-1 Copyright © 2003 Published by Elsevier Ltd. Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
Available online 29 July 2003.
Volume 3, Issue 8, August 2003, Page 463
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem..” ...
Terry S. Singeltary Sr.
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply
IBNC BSE TSE Prion mad cow disease
***however in 1 C-type challenged animal, Prion 2015 Poster Abstracts S67 PrPsc was not detected using rapid tests for BSE.
***Subsequent testing resulted in the detection of pathologic lesion in unusual brain location and PrPsc detection by PMCA only.
*** IBNC Tauopathy or TSE Prion disease, it appears, no one is sure ***
Posted by Terry S. Singeltary Sr. on 03 Jul 2015 at 16:53 GMT
SUNDAY, MARCH 10, 2019
National Prion Disease Pathology Surveillance Center Cases Examined¹ Updated Feb 1, 2019 Variably protease-sensitive prionopathy VPSPr
FRIDAY, OCTOBER 25, 2019
27th ANNUAL REPORT 2018 CREUTZFELDT-JAKOB DISEASE SURVEILLANCE IN THE UK
Variably Protease Sensitive Prionopathy (VPSPr), is of uncertain nosological significance but is presently considered a form of sporadic prion disease, alongside sCJD. The NCJDRSU has so far identified a total of 17 such cases in the UK and is continuing to monitor this form of disease.
SUNDAY, AUGUST 09, 2009
CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009
TUESDAY, AUGUST 18, 2009
BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009
Terry S. Singeltary Sr.
