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My mother was murdered by what I call corporate and political homicide i.e. FOR PROFIT! she died from a rare phenotype of CJD i.e. the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. sporadic, simply meaning from unknown route and source. I have simply been trying to validate her death DOD 12/14/97 with the truth. There is a route, and there is a source. There are many here in the USA. WE must make CJD and all human TSE, of all age groups 'reportable' Nationally and Internationally, with a written CJD questionnaire asking real questions pertaining to route and source of this agent. Friendly fire has the potential to play a huge role in the continued transmission of this agent via the medical, dental, and surgical arena. We must not flounder any longer. ...TSS

Monday, November 06, 2017

Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque

Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque 

Emmanuel E. Comoy, Jacqueline Mikol, Nina Jaffré, Vincent Lebon, Etienne Levavasseur, Nathalie Streichenberger, Chryslain Sumian, Armand Perret-Liaudet, Marc Eloit, Olivier Andreoletti, Stéphane Haïk, Philippe Hantraye & Jean-Philippe Deslys Published online: 02 November 2017 


Exposure of human populations to bovine spongiform encephalopathy through contaminated food has 

resulted in <250 99="" cases="" creutzfeldt-jakob="" disease="" however="" more="" of="" span="" than="" variant="" vcjd="">

infections could have remained silent suggesting a long-term risk of secondary transmission particularly 

through blood. Here, we present experimental evidence that transfusion in mice and non-human primates

of blood products from symptomatic and non-symptomatic infected donors induces not only vCJD, but

also a different class of neurological impairments. These impairments can all be retransmitted to mice with a 

pathognomonic accumulation of abnormal prion protein, thus expanding the spectrum of known prion  

diseases. Our findings suggest that the intravenous route promotes propagation of masked prion variants

according to different mechanisms involved in peripheral replication.


Bovine spongiform encephalopathy (ESE) was widely distributed in Europe and most notably in the UK. Overall, more than 2 million undiagnosed infected cattle would have entered the human food chain1, implying an estimated exposure of 10 million consurners2. However, the fatal variant Creutzfeldt-Jakob disease (vCJD) in humans has fortunately remained rare, with 177 cases in the UK to date (51 in the rest of the world, including 27 in France); the majority of cases were detected between 1995 and 2005, and only three cases from 2012 to 2016. Besides primary contamination through food, inter-human vCJD transmission has been associated with blood transfusions from donors incubating vCJD in the UK, but this has been limited to 4 cases among the 67 recorded recipients of blood from identified vCJD donors (<6 10="" 2003="" 50:50="" a="" addition="" and="" associated="" be="" been="" before="" between="" blood="" by="" case="" contamination="" deleukocytation="" derivatives.="" donations="" extracted="" factor="" for="" from="" has="" implementation="" improvements="" in="" included="" infection="" infectivity="" introduction="" is="" leucocytes="" measures="" nbsp="" no="" occurred="" of="" one="" plasma6="" plasma="" pool="" possible="" preclinical="" presumed="" procedures="" purification="" ratio="" reported="" shared="" silent="" since="" span="" such="" systematic="" techniques="" that="" the="" those="" to="" transfusion="" transmission="" treatment="" vcjd4.="" vcjd="" viii="" was="" with="">

In contrast to the limited prevalence of clinical vCJD, abnormal prion protein (PrPd) was detected in 16 appendices among more than 32,000 samples in a recent anonymized survey of prevalence in the UK population. This suggests an unexpectedly high prevalence (1/2000, 493 per million) of asymptomatic infected subjects that is at least 100-fold higher than that of reported clinical cases7. The development of the disease after an extended period of time, may be several decades as observed with Kuru'8 and iatrogenic CJD9, cannot be excluded. However, the most probable scenario is that after exposure to BSE, more than 99% of infected individuals will remain as silent carriers, possibly for decades. Such a long-term silent infection of lymphoid tissues represents a risk of secondary transmission that is difficult to assess. With regard to blood transfusion, basic calculations suggest that the risk may be in the order of 1000 potentially contaminated blood donations every year in the UK. Moreover, projections assume that the prevalence of clinical and subclinical infections in most of the other countries of Western Europe would be significant, since no more than 10- to 100-fold lower10. According to these levels of exposure, which are much higher than those of several blood-borne viruses, there is continuing cause for concern about the management of blood, blood components and derivatives, and surgical instruments that supports further evaluation of risks from primary BSE and secondary vCJD in relevant experimental models. 

In this study, we aim to explore the risk of prion infection from blood-derived products using both conventional mice susceptible to vCJD11,12 and in non-human primates that are considered to be the ultimate model of the human condition with regard to prions13,14, especially for BSE infection15,16. Neurological impairments are transmitted to recipients in these two animal models using blood infectivity (transfusion of blood products derived from infected donors) and brain infectivity (intravenous exposure to soluble infected material derived from brain tissue). Nevertheless, a low percentage of the affected recipient animals exhibit specific features of vCJD, whereas a much higher proportion of them develops neurological impairments devoid of the classical biochemical and/or pathological features that currently constitute the diagnostic criteria for prion diseases. These atypical impairments are identified as prion disorders by secondary transmission.


Transmission of neurological impairments without PrPres

In a series of independent experiments, we transfused blood products derived from donors exposed to vCJD into 470 wild-type mice and 19 cynomolgus macaques. In parallel, we injected 70 mice and 11 macaques intravenously (IV) with soluble brain extracts derived from BSE- or vCJD-infected donors; the extracts were obtained according to protocols designed to mimic blood infectivity17. As negative controls, animals were sham-inoculated (40 mice and 6 macaques) or exposed to blood or brain products from healthy donors (90 mice and 2 macaques), while positive controls included animals exposed to crude homogenates of infected brains through the intracerebral (IC) (38 mice and 10 macaques) or IV (12 mice and 4 macaques) route.

All the IC- and IV-inoculated positive control animals (50/50 mice and 14/14 macaques) developed vCJD (Fig. 1). Protease-resistant PrPd (PrPres) was detected in their brains using classical biochemical diagnostic methods (ELISA and western blot), as a confirmation of their positive prion infection status, as expected. None of the negative control animals exhibited neurological signs.

After intravenous exposure to exogenous preparations (soluble infected brain extracts) or endogenous preparations (infected blood), a proportion of the animals (94/540 mice and 24/30 macaques) developed fatal neurological impairments with incidences ranging from 10 to 100% depending upon the inoculum. A higher incidence of fatal neurological impairment was obtained in animals exposed to soluble infected brain extracts that were expected to harbour more infectivity than the infected blood. Among the affected animals, classical biochemical diagnostic methods detected PrPres in the brains and spleens of only 41/94 mice and 15/24 macaques (and in none of the asymptomatic animals). We further investigated the neurologically affected animals but PrPres negative (53/94 mice and 9/24 macaques) that corresponded, (depending on the inoculum), to between 9 and 80% of the animals developing neurological impairments (Fig. 1).

vCJD prions induce distinct incomplete vCJD profiles in mice

The 94 neurologically affected mice exposed to infected brain extracts or infected blood exhibited similar neurological signs (general weakness, paresis to paralysis of the lower limbs and tail) to the 50 positive control animals. This was independent of the inocula they received and their expression of PrPres; these animals were thus initially suspected of developing the same prion disease as the positive controls. Seventy-four (80%) of the mice with neurological impairments and similar numbers of mice exposed to infected material and devoid of neurological signs (64 mice considered as apparently negative) and control mice (68 mice including 41 negative control mice considered as healthy) were sampled for histology and for detection of PrPd by immunohistochemistry (Supplementary Table 1).

Among the 94 neurologically affected mice, 29 mice (all PrPres positive) presented a classical vCJD profile: they exhibited significant neuronal lesions (mainly neuronal vacuolation), cerebral and spinal sponjpgorm change (Fig. 2a, b) associated with the accumulation of abnormal PrP (PrPd) in both brain and spinal cord (Fig. 2c) and in their spleen (Supplementary Fig. 1). Seven other animals, that showed accumulation of PrPres but were not sampled for histology, were classified as vCJD (total number of vCJD cases was thus 36).

The 58 other mice exhibited atypical disease phenotypes distinct from vCJD after similar or even longer incubation periods (Fig. 2k). Those disorders appeared as truncated vCJD phenotypes as they presented similar lesions but not the complete spectrum. We classified the animals with atypical neurological impairments into five distinct pathological phenotypes (Fig. 2a) according to their main histological lesions, which may be themselves divided into two main groups according to the presence or absence of PrPd.

The first group included the five remaining PrPres positive animals that we classified as bulbospinal (BS): they exhibited the same pattern of neuronal lesions and PrPd deposits in the whole central nervous system (CNS) as vCJD mice, but spongiform change was restricted to the brainstem and spinal cord (Fig. 2a, d). An accumulation of PrPd in their spleen was detected by biochemical and immunohistochemical methods (Supplementary Fig. 1). In parallel, 10 PrPres negative animals exhibited deposition of PK-sensitive PrPd (accumulation was observed with immunohistochemistry but biochemistry was negative) and spongiform change both of which were strictly limited to their spinal cords (Fig. 2e, f). These animals were thus classified as spinal (S). It was puzzling to observe that 16 supplementary animals, all exposed to blood products from non-human primates, were still alive and not showing neurological impairments at the end of the study (>750 days), but also exhibited accumulation of spinal PrPd, and among them seven had associated spongiform change. We did not, however, include these animals in the total of S phenotypes according to their ages, but classified them as aging spinal, or AS, animals. Those 15 PrPd positive (+16 AS) animals constitute the first group of atypical phenotypes with lesions focused on the spinal cord.

The second group comprised 30 animals that showed lesions restricted to the brain (no lesions of the spinal cord) and an absence of detectable PrPd (Fig. 2g–j). Fifteen of this group exhibited a lesion profile identical to vCJD mice (cerebral phenotype, C), nine animals showed spongiform change limited to the brainstem (brainstem phenotype, B) and six animals only exhibited neuronal vacuolation (neuronal lesions only phenotype, NL).

The 13 remaining PrPres negative animals with neurological signs could not be sampled for histology and thus cannot be specifically subclassified within the S, C, B or NL phenotypes. They were thus classified as non-vCJD. No significant neuronal lesions or spongiform change were observed either in 41 healthy negative control mice sampled for histology (Fig. 2j), sampled at ages corresponding to 171–795 days of incubation, or in 48 among the 446 inoculated animals devoid of neurological signs and considered to be negative (214–762 dpi).

Unexpected syndromes in macaques after transfusion

In cynomolgus macaques (see Supplementary Note 1 and Supplementary Fig. 2 for experimental details), the 29 PrPres positive animals exhibited the expected BSE/vCJD phenotype (Table 1; Supplementary Fig. 3). They included 24 recipients of brain homogenates and 5 of the 19 transfused macaques (26%) that were all exposed to non-deleukocyted blood products from primate donors with high levels of peripheral PrPd. These results confirmed the transmissibility of vCJD by transfusion in primates.

In contrast to the mice, the 9 PrPres negative macaques developed a distinct pattern corresponding to an, as yet to our knowledge, undescribed fatal neurological impairment devoid of the main classical features of vCJD. This disorder has the features of a spinal cord disease that is not usually linked to prion disease. The macaques were exposed either to soluble infected brain material (1/11 animals (9%)) or were transfused (8/19 = 42%) with blood derived from donors with detectable accumulation of PrPd or infectivity in their peripheral organs, including donors with the status of healthy carriers (Supplementary Note 1). Four other animals exposed to some of those blood products still remain asymptomatic 15.5–17 years post inoculation. No neurological impairment was recorded in the four macaques exposed either to blood from healthy donors (negative controls) or to blood samples with no expected infectivity (derived from primate donors infected intracerebrally with BSE/vCJD and devoid of detectable peripheral PrPd).

The 9 macaques that developed this atypical neurological impairment began their long clinical phases (2–6 months) with impaired visual acuity, dysmetry of the forelimbs and they gradually stopped using their hands (Table 1). Hind-limb ataxia appeared after several weeks, followed by progressive proximal paresis of the forelimbs and atrophy of shoulder muscles. Cranial nerve involvement was suspected because of a permanently open mouth, frequent yawning and impaired mobility of the tongue.

The animals exhibited almost no lesions in the cerebral hemispheres: the cortices and basal ganglia were virtually spared; there was moderate rarefaction of cerebellar granule cells but no spongiform change was observed. However, all animals presented severe bulbar and spinal lesions (Fig. 3; Supplementary Fig. 4) and we classified this original pattern as myelopathy.

None of the classical immunohistochemical or biochemical methods, including the latest amplifying methods that are able to detect ultra-low levels of aggregated abnormal PrP with seeding activity (PMCA and RT-QuiC), was able to detect PrPd in the CNS (brain or spinal cord) of any of the nine myelopathic macaques (Fig. 4; Supplementary Figs. 5, 6) except in the macaque that was exposed to the highest blood infectivity (macaque R5 in Figs. 4, 5). At the same time, all tests designed to detect an alternative aetiology to a prion disease for this myelopathy were negative (Supplementary Note 2; Supplementary Tables 2–4).

Primate myelopathy induces incomplete vCJD profiles in mice

Blood samples (plasma or buffy coat, BC) from PrPd negative and PrPd positive myelopathic macaques were injected IV into 72 and 71 Swiss mice, respectively, while similar blood products derived from vCJD macaques and mice were injected into 222 and 105 Swiss mice, respectively. Altogether these mice correspond to the 470 mice exposed to blood products as described above. In parallel, mice were inoculated by intracerebral injection with brain material derived from myelopathic and vCJD macaques (N = 10 and 12, respectively).

Neurological impairment was observed in some mice exposed to brain (5/10, 50%) or blood (8/143, 6%) samples derived from the myelopathic macaques: none of the mice developed a complete vCJD profile, but they exhibited the same incomplete vCJD phenotypes as those described above, including the spinal (S) phenotype with PrPd accumulation in their spinal cords (Figs. 6, 7, details in Supplementary Table 5). These groups also included 62% (10/16) of the AS animals.

mong the four groups of mice exposed to plasma from the different sources, no statistically significant difference (χ2-test) was observed in terms of rates of transmission, of PrPd positive or PrPres positive animals, suggesting that infectivity from plasma is similar in vCJD and myelopathic macaque donors. Conversely, a gradient for the same criteria was observed in the groups exposed to BC samples derived from vCJD mice >vCJD macaques >PrPd positive myelopathic animals (only three AS mice) >PrPd negative myelopathic animals, for which no disease was transmitted: buffy coats from myelopathic macaques appeared to harbour limited infectivity, if any.

Incomplete vCJD profiles are transmissible prion diseases

Transmissibility of incomplete vCJD phenotypes was assessed through IC or IV injection of material from brain, spinal cord and spleen derived from some mice (Fig. 7b; Supplementary Table 5) within the same mouse strains. Almost complete transmission was obtained with the PrPres positive phenotypes (vCJD and BS), with recipients exhibiting PrPres after short incubation periods (Supplementary Fig. 7).

PrPres negative phenotypes also transmitted neurological impairments but with lower rates: the diseased animals exhibited the same incomplete phenotypes but also vCJD, confirming that all the incomplete phenotypes are true prion diseases (see details in Supplementary Note 3). Notably the PrPd positive S phenotype was transmissible and maintained by intracerebral inoculation of CNS tissue or by intravenous administration of spleen tissue.

Among all the transmission studies, the intracerebral route resulted in the preferential development of the complete vCJD phenotype, whereas the intravenous route also induced vCJD but favoured the maintenance of the incomplete phenotypes and notably preferential involvement of the spinal cord (Supplementary Table 6; Supplementary Fig. 8).

Soluble infectivity promotes PrPres negative prion diseases

We combined information on the prion nature of the different neurological impairments, and then detailed the distribution of the different phenotypes within the animals exposed to brain or blood infectivity. The results of this analysis clearly showed that the emergence of atypical prion disease phenotypes correlated with the exposure to soluble infectivity derived from brain or plasma. Indeed, crude brain homogenates induced the expected vCJD phenotypes in all macaque recipients (10/10 IC and 4/4 IV exposed animals), whereas myelopathy occurred in only one recipient (10%) of the corresponding soluble extracts (Fig. 8). Among macaque recipients of highly infectious blood products (R1–R5 and R15–R17), vCJD occurred in 3/3 recipients of whole blood and 2/3 recipients of red blood cell concentrates (RBCC) that still contained plasma and leucocytes (the third recipient developed a myelopathy with PrPd, that may be considered as an intermediate disease), whereas the two recipients of deleukocyted RBCC (only red cells and plasma) developed myelopathy. In addition, the deleukocytation of blood with low infectivity did not impair the transmission of myelopathy (macaques R8–R11).

In mice, the proportions of PrPres negative phenotypes were higher in recipients of plasma than in the recipients of buffy coat, and also in recipients of supernatants than in those animals that received pellets of soluble brain homogenate, whereas all recipients of vCJD-infected crude brain homogenates developed PrPres positive prion disease (Fig. 9a; Supplementary Table 5). Studies on soluble brain extracts were performed in two conventional mice models (Swiss and C57Bl/6 mice) and with two different infectious sources (BSE-infected cattle and primate). In those four models taken together, a complete vCJD presentation was observed in only 41% (28/69) of recipients, while 29% (20/69) exhibited incomplete syndromes. Sixteen animals exhibited the cerebral profile without PrPd while four animals developed the BS profile with cerebral and spinal PrPd. In more detail, the incidence of neurological signs and vCJD phenotypes was higher in Swiss mice than in C57Bl/6 mice; the incidence was also higher with extracts of non-human primate brain than with extracts of cattle brain and higher with pellet samples than with samples of supernatant. Those groups with higher incidence also tended to promote BS profiles, whereas the opposite groups tended to promote cerebral (C) profiles (Supplementary Table 7). No recipient of brain fractions exhibited the S profile.

Peripheral replication pathways select PrPres negative prion

In both experimental models, all the PrPres positive animals exhibited accumulation of PrPd in follicles in the spleen, whereas no animal developing a PrPres negative disease (NL, B, C or S phenotypes in mice, myelopathy in non-human primates) had detectable accumulation of PrPd in their lymphoid organs. We hypothesise that two distinct pathophysiological pathways may coexist (Fig. 9b). Within the classical pathway, associated with aggregated abnormal PrP, peripheral replication occurs at the level of follicular dendritic cells (FDC) in lymphoid organs, and the resulting PrPres positive disease affects the whole CNS following neuroinvasion along afferent nerves. Conversely, infectivity in a soluble form would follow an alternative pathway: peripheral replication would occur at different sites of replication that remain to be defined and lead to PrPres negative disease affecting brain or spinal cord.


The observed prevalence in human populations of primary and secondary (transfusion-transmitted) vCJD clinical cases is very low. This is in contrast to recent estimates suggesting, paradoxically, that there has been massive exposure of the human population2 and that healthy carriers are close to 200-fold greater in number than the reported cases7. Thus, among the 10 million humans exposed in the UK, <0 .5="" a="" all="" among="" an="" and="" applied="" been="" blood="" by="" classical="" develop="" developed="" expected="" experimental="" exposed="" exposure="" furthermore="" have="" here="" high="" human="" in="" independent="" infected="" infectivity.="" infectivity="" is="" leukodepleted="" leukodepletion="" level="" models.="" models="" no="" non-deleukocyted="" non-human="" now="" observed="" of="" only="" people="" population="" primate="" products="" proportion="" protection="" provided="" recipients="" regarding="" replicate="" resulted="" risk="" rodent="" show="" situation="" small="" span="" susceptible="" systematically="" that="" the="" therefore="" these="" to="" transfusion.="" transmission="" two="" underlines="" vcjd.="" vcjd="" was="" we="" were="" which="" will="" with="" would="">

However, in the same experiments, higher proportions (2- to 7-fold more) of recipients developed other fatal neurological impairments, some of them exclusively involving the spinal cord. These unexpected neurological impairments would escape the current criteria for the diagnosis of prion diseases; such criteria include the presence of abnormal PK-resistant PrP associated with spongiform change in the brain (Supplementary Table 8). Nevertheless, we consider that these disorders have a prion aetiology, as they transmit diseases to recipient mice that exhibit the classical features of transmissible spongiform encephalopathies, i.e., accumulation of (PK-resistant or not) PrPd and spongiform change in all or part of the CNS. Similar results were achieved by intravenous administration of soluble material derived from infectious brains, which is an acknowledged model of blood infectivity. Furthermore, it is important to note that the transmission of this atypical prion disease in non-human primates is apparently not prevented by the compulsory leukodepletion step for infected blood.

Interestingly, these atypical prion phenotypes occur after incubation periods similar to vCJD in mice, and even shorter in macaques, suggesting that they are due to different variants. According to our results, the onset of such atypical prion phenotypes, including spinal cord involvement, seemed to be preferentially promoted by the administration of soluble infectivity through the intravenous route, whereas the most commonly used method (administration of crude homogenates via an intracerebral route) is associated with the classical vCJD phenotype. So, we hypothesise that non-protease-resistant soluble infectivity in blood might follow an alternate pathophysiological pathway from the stage of peripheral replication; this pathway, that may even correspond to a direct neuroinvasion as recently described18, remains to be elucidated. Indeed, it has been shown that, in spleen, FDC trap particulate antigens but not soluble antigens of a size similar to PrP monomers19. Prion variants dissociated from PrPres could be selected through such an alternate pathway. The commonly held opinion is that there is a unique signature for the BSE/vCJD prion, which is known to be remarkably stable even after multiple transmissions between species20,21. Reality might be much more complex: the emerging view is that each prion strain exists much like a quasi-species as described for viral and bacterial pathogens. According to this cloud hypothesis22, prions would constitute a dynamic ensemble of different conformations of abnormal PrP (PrPd). Some conformations would correspond to forms of PrP detectable on the basis of their resistance to proteolysis, so called PrPres, whereas other conformations, that are oligomeric and until now undetectable by biochemical techniques, would constitute the most toxic and infectious entities. An even greater complexity may arise from the capacity of cellular PrP to interact naturally with several molecules including non-coding RNA, DNA or Aβ23,24,25.

In this hypothesis, PrPres and infectivity/toxicity can be dissociated26,27,28,29,30,31. We previously reported the first obvious dissociation following primary transmission of BSE to mice11. Following intracerebral inoculation, all animals developed similar neurological signs but more than 50% had no detectable PrPres. On secondary and tertiary transmissions, however, the proportion of PrPres positive animals gradually increased to almost 100%. Recent communications suggest that a similar situation might exist in other models of experimental exposure to prions involving swine32 and cattle33. In the present study, we used two animal models and blood transfusion to demonstrate a complete dissociation that could be maintained on successive passages. The panel of incomplete syndromes that we have observed in both mice and non-human primates suggests that the phenotypic expression of vCJD prion infection may vary. The recent description of vCJD in codon 129 heterozygous patients34 may even expand this possible spectrum of clinical heterogeneity. Such variation ranges from the status of healthy carrier to classical vCJD and includes clinical-pathological presentations that would be excluded from the diagnosis of prion disease according to current criteria.

The complete dissociation that we observed here, with toxicity in the absence of PrPres, counterbalances the observations made using PrPres amplification techniques. Such PrPres amplification techniques generate large amounts of PrPres but little or none of the toxic and infectious form of PrP. RT-QuiC is reported to be able to amplify over 1012 the quantity of PrPres in scrapie samples by converting recombinant cellular PrP (PrPc) produced in bacteria, but almost no infectivity is generated35. PMCA, which uses normal brain as a substrate for the conversion of PrPc, is able to maintain infectivity during successive cycles despite serial dilutions and can even generate infectivity de novo from normal mouse and hamster brains36,37. However up to more than 99% of the PrPres generated, de novo is not infectious (dissociation of at least two logs between infectivity and de novo generated PrPres)38. None of these techniques, which are increasingly used for the diagnosis of human prion diseases, was able to generate PrPres from our infectious PrPres negative samples.

The neurological impairment described here in macaques appears to be unique as it has not been reported previously. However, Holznagel et al.39 reported a specific pattern of spinal cord involvement in cynomolgus macaques exposed orally to BSE. These animals remained asymptomatic, but they exhibited atypical deposition of PrPd that was transmissible to bovinized mice39. Necrotic myelopathies have been described in humans that share clinical and pathological features with the primates in the present study40. The neuropathological features in macaques (lesions of both the cervical anterior horns and the spinal nuclei of the trigeminal nerves) resembled focal forms of subacute necrotising encephalomyelopathy as previously reported in Leigh syndrome41 but their posterior columns showed tract degeneration. However, as in Leigh syndrome, dysfunction of energy metabolism may be suspected42. Moreover, the atypical myelopathy in macaques shows similarities to other human myelopathies that range from neuromyelitis optica spectrum disorders (NMOSD), for which inclusion criteria are wide43, to the more recently described FOSMN44 and to certain forms of amyotrophic lateral sclerosis like FLAIL arm syndrome45. This latter syndrome presents as a pure lower motor neuron disorder that then evolves after a number of years to include upper motor neuron lesions46, a feature that we did not observe in our primates. However, in the absence of suitable nursing facilities, these primates were killed relatively early for ethical reasons.

This report strongly suggests that prions might remain hidden in the population and as the majority of healthy carriers may never develop a prion disease, an even greater proportion of contaminated individuals may never be diagnosed as healthy carriers, currently diagnosed according to the presence of PrPd in their lymphoid tissues. Moreover, should such atypical agents or their subsequent passages in humans lead to neurological impairment, there is a significant risk that they would not be diagnosed as related to prion infection in the absence of detectable PrPres and a quasi-exclusive spinal involvement. Our results enlarge the range of prion diseases that is already no longer restricted to PrPres positive diseases that target the brain47,48,49.

In conclusion, the range of incomplete syndromes that we observed between healthy carriers and typical vCJD indicates that multiple forms of prion variants can coexist and may emerge in different forms depending upon the conditions under which transmission occurred. This has obvious consequences for public health, and questions the uniqueness of the BSE/vCJD strain50 and our capacity to detect and prevent all infectious forms of prion disease. 

''On secondary and tertiary transmissions, however, the proportion of PrPres positive animals gradually increased to almost 100%. Recent communications suggest that a similar situation might exist in other models of experimental exposure to prions involving swine32 and cattle33. '' 

''Experimental transfusion of variant CJD-infected blood reveals previously uncharacterised prion disorder in mice and macaque''

Holy Mad Cow Batman!

10,000,000 Pounds of Blood Laced Meat and Bone Meal in Commerce in the USA 2007




Bulk cattle feed made with recalled Darling’s 85% Blood Meal, Flash Dried, Recall # V-024-2007


Cattle feed delivered between 01/12/2007 and 01/26/2007


Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007. Firm initiated recall is ongoing.


Blood meal used to make cattle feed was recalled because it was cross-contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.


42,090 lbs.


WI ___________________________________




The firm does not utilize a code - only shipping documentation with commodity and weights identified.


Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.


Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.


9,997,976 lbs.


ID and NV




FDA 589.2000, Section 21 C.F.R. Animal Proteins Prohibited in Ruminant Feed WARNING Letters and FEED MILL VIOLATIONS OBSERVATIONS 2017 to 2006



''I have a neighbor who is a dairy farmer. He tells me that he knows of several farmers who feed their cattle expired dog food. These farmers are unaware of any dangers posed to their cattle from the pet food contents. For these farmers, the pet food is just another source of protein.''



EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of the United States of America (USA) a review 2017


JAVMA NEWS Atypical BSE found in Alabama cow September 01, 2017


TUESDAY, JULY 18, 2017 

USDA announces Alabama case of Bovine Spongiform Encephalopathy Alabama

THURSDAY, JULY 20, 2017 

USDA OIE Alabama Atypical L-type BASE Bovine Spongiform Encephalopathy BSE animal feeds for ruminants rule, 21 CFR 589.200

SUNDAY, JULY 23, 2017

atypical L-type BASE Bovine Amyloidotic Spongiform Encephalopathy BSE TSE PRION

SUNDAY, JULY 23, 2017

Experimental Infection of Cattle With a Novel Prion Derived From Atypical H-Type Bovine Spongiform Encephalopathy

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 5, Article number: 11573 (2015)


Download Citation

EpidemiologyNeurological manifestationsPrion diseases

Received: 16 February 2015

Accepted: 28 May 2015

Published online: 30 June 2015


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.


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.


***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.***

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. 

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 

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.


Creutzfeldt Jakob Disease United States of America USA and United Kingdom UK Increasing and Zoonotic Pontential From Different Species


*** Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States revisited 2017

Singeltary et al


Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein 

Here we go folks. AS predicted. THIS JUST OUT !

Saturday, June 13, 2009

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009 

Sunday, August 09, 2009

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009 

FRIDAY, AUGUST 11, 2017 

Infectivity in bone marrow from sporadic CJD patients

Bioassays in transgenic mice expressing the human prion protein revealed the presence of unexpectedly high levels of infectivity in the bone marrow from seven out of eight sCJD cases. These findings may explain the presence of blood-borne infectivity in sCJD patients. They also suggest that the distribution of prion infectivity in peripheral tissues in sCJD patients could be wider than currently believed, with potential implications for the iatrogenic transmission risk of this disease. 

*** Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery *** 

Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892. 

Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them. 


*** Minimise transmission risk of CJD and vCJD in healthcare settings Updated 10 August 2017


Subject: ***CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat

CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat 

Chronic Wasting Disease (CWD) 


If CWD could spread to people, it would most likely be through eating of infected deer and elk. In a 2006-2007 CDC survey of U.S. residents, nearly 20 percent of those surveyed said they had hunted deer or elk and more than two-thirds said they had eaten venison or elk meat. However, to date, no CWD infections have been reported in people. 

Hunters must consider many factors when determining whether to eat meat from deer and elk harvested from areas with CWD, including the level of risk they are willing to accept. Hunters harvesting wild deer and elk from areas with reported CWD should check state wildlife and public health guidance to see whether testing of animals is recommended or required in a given state or region. In areas where CWD is known to be present, CDC recommends that hunters strongly consider having those animals tested before eating the meat. 

Tests for CWD are monitoring tools that some state wildlife officials use to look at the rates of CWD in certain animal populations. Testing may not be available in every state, and states may use these tests in different ways. A negative test result does not guarantee that an individual animal is not infected with CWD, but it does make it considerably less likely and may reduce your risk of exposure to CWD. 

To be as safe as possible and decrease their potential risk of exposure to CWD, hunters should take the following steps when hunting in areas with CWD: 

Do not shoot, handle or eat meat from deer and elk that look sick or are acting strangely or are found dead (road-kill). When field-dressing a deer: Wear latex or rubber gloves when dressing the animal or handling the meat. Minimize how much you handle the organs of the animal, particularly the brain or spinal cord tissues. Do not use household knives or other kitchen utensils for field dressing. Check state wildlife and public health guidance to see whether testing of animals is recommended or required. Recommendations vary by state, but information about testing is available from many state wildlife agencies. Strongly consider having the deer or elk tested for CWD before you eat the meat. If you have your deer or elk commercially processed, consider asking that your animal be processed individually to avoid mixing meat from multiple animals. If your animal tests positive for CWD, do not eat meat from that animal. The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service regulates commercially farmed deer and elk. The agency operates a national CWD herd certification program. As part of the voluntary program, states and individual herd owners agree to meet requirements meant to decrease the risk of CWD in their herds. Privately owned herds that do not participate in the herd certification program may be at increased risk for CWD. 

Page last reviewed: August 17, 2017 Page last updated: August 17, 2017 Content source: Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of High-Consequence Pathogens and Pathology (DHCPP) 

 > 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 


*** 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).*** 

Molecular Barriers to Zoonotic Transmission of Prions 

*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein. 

*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype. 


CDC Now Recommends Strongly consider having the deer or elk tested for CWD before you eat the meat 

Prion 2017 Conference Abstracts CWD


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. 





 TUESDAY, JUNE 13, 2017


First evidence of intracranial and peroral transmission of Chronic Wasting Disease (CWD) into Cynomolgus macaques: a work in progress

TUESDAY, JULY 04, 2017


TUESDAY, JUNE 13, 2017

PRION 2017 CONFERENCE ABSTRACT Chronic Wasting Disease in European moose is associated with PrPSc features different from North American CWD

Wednesday, May 24, 2017 

PRION2017 CONFERENCE VIDEO UPDATE 23 – 26 May 2017 Edinburgh UPDATE 1 

SATURDAY, JULY 29, 2017 

Risk Advisory Opinion: Potential Human Health Risks from Chronic Wasting Disease CFIA, PHAC, HC (HPFB and FNIHB), INAC, Parks Canada, ECCC and AAFC 

National Prion Center could lose all funding just as concern about CWD jumping to humans rises

SATURDAY, JULY 15, 2017 

*** National Prion Center could lose all funding just as concern about CWD jumping to humans rises


*** RE-P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study

***suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD. ***

P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study

Paul Brown1, Diane Ritchie2, James Ironside2, Christian Abee3, Thomas Kreil4, and Susan Gibson5 1NIH (retired); Bethesda, MD USA; 2University of Edinburgh; Edinburgh, UK; 3University of Texas; Bastrop, TX USA; 4Baxter Bioscience; Vienna, Austria; 5University of South Alabama; Mobile, AL USA

Five vCJD disease transmissions and an estimated 1 in 2000 ‘silent’ infections in UK residents emphasize the continued need for information about disease risk in humans. A large study of blood component infectivity in a non-human primate model has now been completed and analyzed. Among 1 GSS, 4 sCJD, and 3 vCJD cases, only GSS leukocytes transmitted disease within a 5–6 year surveillance period. A transmission study in recipients of multiple whole blood transfusions during the incubation and clinical stages of sCJD and vCJD in ic-infected donor animals was uniformly negative. These results, together with other laboratory studies in rodents and nonhuman primates and epidemiological observations in humans, suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD. The issue of decades-long incubation periods in ‘silent’ vCJD carriers remains open.

ran across an old paper from 1984 ;

***The occurrence of contact cases raises the possibility that transmission in families may be effected by an unusually virulent strain of the agent. ***

snip...see full text ;

Variably protease-sensitive prionopathy (VPSPr), a recently identified and seemingly sporadic human prion disease, is distinct from Creutzfeldt-Jakob disease (CJD) but shares features of Gerstmann-Sträussler-Scheinker disease (GSS). However, contrary to exclusively inherited GSS, no prion protein (PrP) gene variations have been detected in VPSPr, suggesting that VPSPr might be the long-sought sporadic form of GSS. snip...

In conclusion, we propose that VPSPr is transmissible and, therefore, is an authentic prion disease. However, transmissibility cannot be sustained through serial passages presumably because human PrPC (or the mouse brain environment) cannot efficiently convert and propagate the VPSPr PrPSc species. If this is the case, uncovering the properties of human PrP that are required to replicate more efficiently the prion strains associated with VPSPr may help clarify the PrPSc mode of formation in this intriguing disease. 

Friday, January 10, 2014

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???


Case report Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report TEXAS 


OR WAS IT $$$ 


GSS Gerstmann-Sträussler-Scheinker disease with atypical presentation


Blood-derived amyloid-β protein induces Alzheimer’s disease pathologies

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. 

Tracking spongiform encephalopathies in North America

Xavier Bosch

Published: August 2003


“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.”

49-year-old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease (CJD). So he decided to gather hundreds of documents on transmissible spongiform encephalopathies (TSE) and realised that if Britons could get variant CJD from bovine spongiform encephalopathy (BSE), Americans might get a similar disorder from chronic wasting disease (CWD) the relative of mad cow disease seen among deer and elk in the USA. Although his feverish search did not lead him to the smoking gun linking CWD to a similar disease in North American people, it did uncover a largely disappointing situation.

Singeltary was greatly demoralised at the few attempts to monitor the occurrence of CJD and CWD in the USA. Only a few states have made CJD reportable. Human and animal TSEs should be reportable nationwide and internationally, he complained in a letter to the Journal of the American Medical Association (JAMA 2003; 285: 733). "I hope that the CDC does not continue to expect us to still believe that the 85% plus of all CJD cases which are sporadic are all spontaneous, without route or source."

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.

Until recently, CWD was thought to be confined to the wild in a small region in Colorado. But since early 2002, it has been reported in other areas, including Wisconsin, South Dakota, and the Canadian province of Saskatchewan. Indeed, the occurrence of CWD in states that were not endemic previously increased concern about a widespread outbreak and possible transmission to people and cattle.

To date, experimental studies have proven that the CWD agent can be transmitted to cattle by intracerebral inoculation and that it can cross the mucous membranes of the digestive tract to initiate infection in lymphoid tissue before invasion of the central nervous system. Yet the plausibility of CWD spreading to people has remained elusive.

Part of the problem seems to stem from the US surveillance system. CJD is only reported in those areas known to be endemic foci of CWD. Moreover, US authorities have been criticised for not having performed enough prionic tests in farm deer and elk.

Although in November last year the US Food and Drug Administration issued a directive to state public-health and agriculture officials prohibiting material from CWD-positive animals from being used as an ingredient in feed for any animal species, epidemiological control and research in the USA has been quite different from the situation in the UK and Europe regarding BSE.

"Getting data on TSEs in the USA from the government is like pulling teeth", Singeltary argues. "You get it when they want you to have it, and only what they want you to have."

Norman Foster, director of the Cognitive Disorders Clinic at the University of Michigan (Ann Arbor, MI, USA), says that "current surveillance of prion disease in people in the USA is inadequate to detect whether CWD is occurring in human beings"; adding that, "the cases that we know about are reassuring, because they do not suggest the appearance of a new variant of CJD in the USA or atypical features in patients that might be exposed to CWD. However, until we establish a system that identifies and analyses a high proportion of suspected prion disease cases we will not know for sure". The USA should develop a system modelled on that established in the UK, he points out.

Ali Samii, a neurologist at Seattle VA Medical Center who recently reported the cases of three hunters "two of whom were friends" who died from pathologically confirmed CJD, says that "at present there are insufficient data to claim transmission of CWD into humans"; adding that "[only] by asking [the questions of venison consumption and deer/elk hunting] in every case can we collect suspect cases and look into the plausibility of transmission further". Samii argues that by making both doctors and hunters more aware of the possibility of prions spreading through eating venison, doctors treating hunters with dementia can consider a possible prion disease, and doctors treating CJD patients will know to ask whether they ate venison.

CDC spokesman Ermias Belay says that the CDC "will not be investigating the [Samii] cases because there is no evidence that the men ate CWD-infected meat". He notes that although "the likelihood of CWD jumping the species barrier to infect humans cannot be ruled out 100%" and that "[we] cannot be 100% sure that CWD does not exist in humans& the data seeking evidence of CWD transmission to humans have been very limited". 

26 March 2003 

Terry S. Singeltary, retired (medically) CJD WATCH 

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc? 

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. 


2001 FDA CJD TSE Prion Singeltary Submission 

Terry S. Singeltary Sr.