A novel subtype of sporadic Creutzfeldt–Jakob disease with PRNP codon 129MM genotype and PrP plaques
Acta Neuropathol. 2023; 146(1): 121–143.
Published online 2023 May 8. doi: 10.1007/s00401-023-02581-1
PMCID: PMC10166463
PMID: 37156880
A novel subtype of sporadic Creutzfeldt–Jakob disease with PRNP codon 129MM genotype and PrP plaques
Rabeah Bayazid,1 Christina Orru’,6 Rabail Aslam,1 Yvonne Cohen,1 Amelia Silva-Rohwer,1,5 Seong-Ki Lee,2 Rossana Occhipinti,2 Qingzhong Kong,1,5 Shashirekha Shetty,1,5 Mark L. Cohen,1,5 Byron Caughey,6 Lawrence B. Schonberger,7 Brian S. Appleby,1,3,4,5 and Ignazio Calicorresponding author1,5
The presence of amyloid kuru plaques is a pathological hallmark of sporadic Creutzfeldt–Jakob disease (sCJD) of the MV2K subtype. Recently, PrP plaques (p) have been described in the white matter of a small group of CJD (p-CJD) cases with the 129MM genotype and carrying resPrPD type 1 (T1). Despite the different histopathological phenotype, the gel mobility and molecular features of p-CJD resPrPD T1 mimic those of sCJDMM1, the most common human prion disease. Here, we describe the clinical features, histopathology, and molecular properties of two distinct PrP plaque phenotypes affecting the gray matter (pGM) or the white matter (pWM) of sCJD cases with the PrP 129MM genotype (sCJDMM). Prevalence of pGM- and pWM-CJD proved comparable and was estimated to be ~ 0.6% among sporadic prion diseases and ~ 1.1% among the sCJDMM group. Mean age at onset (61 and 68 years) and disease duration (~ 7 months) of pWM- and pGM-CJD did not differ significantly. PrP plaques were mostly confined to the cerebellar cortex in pGM-CJD, but were ubiquitous in pWM-CJD. Typing of resPrPD T1 showed an unglycosylated fragment of ~ 20 kDa (T120) in pGM-CJD and sCJDMM1 patients, while a doublet of ~ 21–20 kDa (T121−20) was a molecular signature of pWM-CJD in subcortical regions. In addition, conformational characteristics of pWM-CJD resPrPD T1 differed from those of pGM-CJD and sCJDMM1. Inoculation of pWM-CJD and sCJDMM1 brain extracts to transgenic mice expressing human PrP reproduced the histotype with PrP plaques only in mice challenged with pWM-CJD. Furthermore, T120 of pWM-CJD, but not T121, was propagated in mice. These data suggest that T121 and T120 of pWM-CJD, and T120 of sCJDMM1 are distinct prion strains. Further studies are required to shed light on the etiology of p-CJD cases, particularly those of T120 of the novel pGM-CJD subtype.
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Here, we describe the detailed disease phenotype and distinctive molecular features of PrPD associated with the pWM-CJD group and novel pGM-CJD subtype. These findings are important as they point toward the distinction of two human prion diseases by divergent PrP plaque phenotypes, and highlight the importance of a careful histopathological examination, with special attention to the cerebellar cortex.
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Beyond sporadic CJD, PrP plaques, including florid plaques and other less common types of plaques, have been described in iCJD, kuru, and variant CJD in humans, or in bovine spongiform encephalopathy (BSE) and chronic wasting disease (CWD) in animals [13, 16, 30, 43, 72]. These prion diseases are readily transmissible to certain transgenic mice and to humans [17, 19, 34, 69]. Furthermore, there are concerns about whether CWD prions can infect humans, as humans are exposed to CWD in several states [29]. Plaques are also observed in genetic prion diseases, such as Gerstmann-Sträussler-Scheinker syndrome (GSS) [18].
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Discussion Prevalence of United States p-CJD We have characterized the clinico-histopathological and molecular features of 21 US p-CJD cases. Taking into account the 14 p-CJD individuals of the retrospective study, the prevalence of each p-CJD subtype is 1.13% among definite sCJDMM cases, or 0.59% among all sporadic prion diseases. The 0.59% prevalence is higher than the 0.17% of iCJD (P = 0.18), but lower than sporadic fatal insomnia (sFI) (1.35%, P = 0.059), sCJDVV1 (1.52%, P = 0.027), and variably protease-sensitive prionopathy (VPSPr) (1.78%, P = 0.0078) [23, 46, 54, 56]. The identification of 7 additional pWM-CJD cases suggests that this subtype is the most common of the two. Furthermore, the pWM-CJD subtype has been previously described by European and Japanese laboratories [4, 26, 33, 63], whereas a gap exists between our description of pGM-CJD and the lack of similar reports in the context of idiopathic CJD [35].
Our study indicates that pGM-CJD should be searched in cases of the -MM2 and -MM1-2 sCJD subtypes. On the contrary, 10 pWM-CJD cases (71%) belonged to the -MM1 subtype, and only two were diagnosed as -MM2 or -MM1-2 [8]. These prevalences are consistent with those of non-US pWM-CJD cases [4, 26, 33, 63].
Clinical and histopathological features of US- and non-US pWM-CJD patients Data from our case series suggests that there may be slight clinical differences between p-CJD and conventional sCJDMM cases. p-CJD cases may present more commonly with cognitive and psychiatric symptoms and less commonly with cerebellar symptoms compared to sCJDMM cases. Additionally, positive CSF 14–3-3 analyses were less frequent in p-CJD cases, and these cases may be less likely to have basal ganglia involvement on brain MRI. These slight differences fall within the expected clinical heterogeneity of CJD and did not appear to affect the clinical diagnoses of these subjects [1]. Interpretation of the clinical phenotype of p-CJD is limited by the amount and type of clinical information that is collected by the NPDPSC. Although clinical phenotypes can sometimes vary across different human prion strains, they are unlikely to be a reliable indicator of strain differences in isolation. Examples are the prominent neuropsychiatric symptoms observed in both vCJD and young onset sCJD and MRI findings suggestive of sCJD in a case of vCJD that was heterozygous at codon 129 [2, 47]. Clinical features have been shown to be heterogeneous in non-US pWM-CJD cases [63]. While age at onset of US and non-US (~ 65 years) pWM-CJD cases does not differ significantly, disease duration was 3-times longer in non-US cases (21 ± 12 months; P < 0.02) [4, 26, 33, 63]. The significantly different disease duration is probably due to more extensive medical care in Asia.
The US pWM-CJD histotype mimicked that of non-US pWM-CJD cases [4, 26, 33, 63]. We and others have recently shown that CAA is a major feature of Aβ pathology in patients with iCJD, but not of age-matched sCJD cases [10, 28, 32, 59]. Although the US p-CJD cases were significantly older than US sCJDMM cases [10], CAA prevalence did not differ between the two diseases. These results point to an age-dependent Aβ pathology in US p-CJD.
US pGM-CJD, sporadic CJD and iCJD cases with PrP plaque pathology: a review of the literature PrP plaques populated the cerebellar cortex in pGM-CJD with the exception of one case in which rare PrP plaques affected the occipital cortex. The spread of PrP plaques to the occipital lobe does not seem to be the result of a protracted disease duration since death occurred two months after clinical presentation. Two pGM-CJD cases showed target-like PrP formations. Whether these “loose plaques” contains PrP fibrils remains to be determined [67]. Also, the presence of only rare diffuse Aβ plaques in these patients is against the hypothesis that target-like PrP is the result of an enhancement of PrP around or within Aβ plaques [10].
We have searched in the literature for the presence of PrP plaques in the gray matter of patients with sporadic prion disease linked to codon 129MM genotype; three cases were found. In the first report, a 54-year-old neurosurgeon with an 18-month disease course and sleep disturbances harbored PrP plaques in the cerebral cortex. Inoculation of brain homogenates from this patient to chimpanzee and squirrel monkeys lead to prion disease. However, the human histotype was not fully reproduced by these primates as kuru-type plaques were not detected in the brain of the affected animals [64]. In another study, a 75-year-old woman with an 11-month clinical course, underwent neurosurgery without dura mater about 14 years before the onset of clinical symptoms. At autopsy, “congophilic amyloid plaques” were noted in the cerebellar cortex [31]. Although both patients were originally diagnosed as being sporadic, a subsequent study suggested these two cases had an iatrogenic prion disease. This conclusion, which stems from a known iatrogenic risk factor in one of the cases (neurosurgery), was supported by an in vivo study [35]. The third case is that of a 40-year-old woman with no known history of iatrogenic exposure who was alive at the time of the brain biopsy, which occurred ~ 2.5 years after the appearance of clinical disease. This patient presented with dementia, showed a “conspicuous” number of PrP plaques in the occipital cortex, and was 129MM [45]. To our knowledge, these cases were free of florid plaques.
In our pGM-CJD case 5, clusters of florid plaques were noted in the cerebellum. Our pGM-CJD case 5, is a 57-year-old male with sensory symptoms (numbness, tingling, and pain in the fingers) at presentation. Case 5 did not have a history of venison consumption, blood transfusion, travel to any BSE-exposed countries, or known surgical history. It should be emphasized that disease onset with sensory symptoms can be a clinical presentation observed in vCJD; however, case 5’s brain MRI demonstrated restricted diffusion abnormalities in the cortex and caudate that is typical for sCJD. Additionally, the illness duration of 2 months is shorter than typically reported in vCJD. The resPrPD glycotype of case 5 resembles that of sCJD.
The presence of florid plaques has been described in a 70-year-old Slovenian female who presented with psychiatric symptoms at the age of ~ 68 years, and had traveled to the UK at a time of BSE pandemic. The patient was of the 129MV genotype and harbored resPrPD T2. Despite the presence of florid plaques and several clinical features overlapping with vCJD, the authors concluded that the patient’s atypical phenotype was likely due to the known heterogeneity of the -MV2 subtype [6, 49, 57]. The resPrPD glycotype of this patient mimicked that of sCJD, characterized by the predominance of the monoglycosylated resPrPD isoform. By contrast, the over-representation of the diglycosylated resPrPD isoform is a feature of vCJD, and is independent of the codon 129 genotype [47, 71]. Florid plaques have been reported in patients with iCJD linked to the 129MM genotype (iCJDMM) [13, 40, 42, 66]. We have described a US growth hormone iCJDMM (GH-iCJDMM) case with a complex PrP plaque pathology. In addition, this patient showed laminar spongiform degeneration, PrP immunostaining with diffuse, plaque-like and perineuronal patterns, and pericellular PrP [13]. Thus, the presence of PrP plaques is the only common histopathological feature of the US GH-iCJDMM and pGM-CJD. Moreover, PrP plaque pathology of the US GH-iCJDMM case was significantly more severe.
Finally, conflicted results are shown in the literature regarding the gel mobility of the unglycosylated resPrPD of iCJDMM cases with PrP plaques. In one case report, resPrPD of DM-iCJD migrated about 1 kDa more than the ~ 21 kDa of sCJDMM1 [42]. Similar results were observed in one US GH-iCJD [10, 13], two atypical iCJD [35], Japanese DM-iCJD [34], and one UK GH-iCJD case[60]. In two other studies, resPrPD of iCJD and sCJDMM1 showed similar gel mobility [20, 66]. Notably, 10 of 11 French iCJDMM cases harbored “Type 1” and only one case “type i” (or type “intermediate”, corresponding to a resPrPD fragment of ~ 20 kDa) [20]. Since the buffer pH and the use of other stringent experimental conditions are important tools in assessing the gel mobility of resPrPD, unified experimental conditions should be used to characterize the molecular features of atypical cases that are suspected of an iatrogenic etiology (Fig. S10).
Molecular features of T1 and T2 of US p-CJD The electrophoretic profile of resPrPD T1 and its anatomical distribution are major differences of p-CJD subtypes. Although T121−20 was noted in ~ 55% of the cases, its prevalence is likely to be higher if a more extensive sampling of subcortical brain regions is carried out. T121−20 was occasionally detected in the cerebral cortex, but never found in the cerebellum. These data suggest a tropism of PrPD for different neuronal cell types, and high accessibility of T121 to subcortical regions, where PrPC is likely to be converted to PrPD T121 at a higher rate than T120. This hypothesis is supported by the fact that our buffer pH (8.0) favors the formation of T120 [8, 9, 50]. Furthermore, it seems unlikely that T2 affects T1 distribution in subcortical regions, as the amount of T2 distribution in the two p-CJD subtypes was virtually identical. The fact that T120 of pGM-CJD and sCJDMM1 share similar GdnHCl1/2 values based on the CSSA, does not necessarily indicate that T120 in these two diseases belong to the same prion strain. This can be demonstrated by the similar GdnHCl1/2 indexes of T120 and T2 associated with sCJDVV1 and -VV2, respectively [14]. In previous studies, RT-QuIC assays have revealed some significant differences in the means of kinetic values obtained from certain sCJD subtypes [21]. In this study, we saw modest differences in the overall mean times to threshold between pWM-CJD T1 and pGM-CJD T2 brain specimens, but the relevance of such differences is unclear because they could be explained by relative seed concentration and distinct seed structures. A second major molecular difference, is the higher proportion of T2 and sCJDMM2-like histopathological features in pGM-CJD, which exceeded that of pWM-CJD by ~ 3- and twofold, respectively. Despite the significantly higher proportion of T2 in pGM-CJD, T120 is better represented than T2 overall, and the bulk of PrP plaque pathology is in the cerebellum, which harbors only T120 by western blot in most cases. Case 7, with an overall T2 representation of only 3%, deserves a separate analysis. Unlike the other pGM-CJD cases, rare PrP plaques populated only the granular layer. This may indicate that the presence of T2 is required for a more severe and/or widespread distribution of PrP plaques, and that T2 aggregates are preferentially sequestered in the amyloid core [68]. Furthermore, cerebellar T1 aggregates may be less compact and readily disaggregate following proteolytic digestion and standard denaturation procedures [37].
Do T121, T120 and T2 of pWM-CJD have strains properties? Transmission studies are a gold standard to gain insights on disease mechanism of neurodegeneration. From our bioassay we can reach three conclusions. First, only pWM-CJD T120 propagates in TgHuPrPGly+/+, generating amyloid plaques. Although we did not perform a second passage, T120 of pWM-CJD and sCJDMM1 likely represent different prion strains. The lack of T2 in these mice indicates that T120 is a faster replicating prion strain [8, 52] (Table (Table1).1). Second, T121 could be a different human strain, as it did not propagate in the host. One possible, but perhaps unlikely, explanation is that T121 in the cerebral cortex (where the brain homogenates was injected), may be unable to convert PrPC into PrPD; or that conversion by T121 is inefficient and occurs at a rate that is several orders of magnitudes lower than that of T120. Recently, we have shown that T121 associated with sCJDVV1 faithfully propagates in the TgHuPrP-129VV mouse brain and that inoculation of T121−20 to the same mouse line generates T121 [11]. However, attempts to transmit T121 to TgHuPrP-129MM mice failed on first and second passages. Altogether, the present data and those of Cali et al. [11] suggest that T121 of pWM-CJD and sCJDVV1 have distinct molecular features, as pWM-CJD T121 does not replicate in TgHuPrP-129MM mice, whereas sCJDVV1 T121 faithfully propagates to TgHuPrP mice with the same genotype (129VV). It would be important to assess whether T121 pWM-CJD faithfully transmits disease to TgHuPrP-129VV mice. Lastly, pWM-CJD injected into TgHuPrPGly+/– mice generated T2 and PrP plaques. These data suggest that the lack of glycosylated PrP isoforms, even in one allele, is sufficient to favor T2 propagation, and therefore overturn strain selection by the host. The incomplete glycosylation may also explain the more complex PrP plaque pathology. Although the formation of PrP plaques in TgHuPrPGly+/– mice may be the result of the partial glycosylation, the presence of immature plaques in the cerebellar white matter argues for a role of T2 (present in the inoculum) in PrP plaque formation. A minority of TgHuPrPGly+/– mice were accessible to T120 of sCJDMM1 but the incubation time was longer than in TgHuPrPGly+/+ mice. Overall, our data suggest that glycans play a protective role in these mice [65, 73]. Although the partial absence of glycans accelerates T2 replication at the expenses of T120, it should be emphasized that T1 in sCJDMM patients is significantly better represented than T2.
Conclusions
We have characterized the clinical, histopathological, and molecular properties of two human prion diseases with distinct PrP plaque pathology and divergent PrPD molecular features. While pWM-CJD cases are readily identifiable due to the presence of PrP plaques on a white background, pGM-CJD cases may be more difficult to detect. If pGM-CJD is a sporadic prion disease, this phenotype should be identified by other prion Surveillance Centers. Nevertheless, the lack of major reports on pGM-CJD by other countries is puzzling as both plaque histotypes have similar prevalences in the United States. If these cases are the result of acquired prion disease, their route of transmission is not apparent and not due to any recognized or currently hypothesized acquired prion disease/risk factors. While one major goal of this study is to contribute to the identification of atypical or novel histotypes (or novel prion diseases), it is important to identify new markers of iatrogenic disease. Meanwhile, it seems appropriate to classify pGM-CJD and pWM-CJD as sporadic prion diseases. Additionally, in vitro and in vivo experiments are needed to further dissect the molecular features of p-CJD PrPD with the aim of gaining insights on the mechanisms governing these disorders.
1999
''I have several autopsies, stating kuru type amyloid plaques, one of the victims was 41 years of age.''
US scientists develop a possible test for BSE
BMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7220.1312b (Published 13 November 1999)
Cite this as: BMJ 1999;319:1312
Rapid Response:
Re: vCJD in the USA * BSE in U.S.
15 November 1999
Terry S Singeltary
NA
medically retired
In reading the recent article in the BMJ about the potential BSE tests being developed in the U.S. and Bart Van Everbroeck reply. It does not surprize me, that the U.S. has been concealing vCJD. There have been people dying from CJD, with all the symptoms and pathological findings that resemble U.K. vCJD for some time. It just seems that when there is one found, they seem to change the clarical classification of the disease, to fit their agenda. I have several autopsies, stating kuru type amyloid plaques, one of the victims was 41 years of age. Also, my Mom died a most hideous death, Heidenhain Variant Creutzfeldt Jakob disease. Her symptoms resemble that of all the U.K. vCJD victims. She would jerk so bad at times, it would take 3 of us to hold her down, while she screamed "God, what's wrong with me, why can't I stop this." 1st of symptoms to death, 10 weeks, she went blind in the first few weeks. But, then they told me that this was just another strain of sporadic CJD. They can call it what ever they want, but I know what I saw, and what she went through.
Sporadic, simply means, they do not know.
My neighbors Mom also died from CJD. She had been taking a nutritional supplement which contained the following;
vacuum dried bovine BRAIN, bone meal, bovine EYE, veal bone, bovine liver powder, bovine adrenal, vacuum dried bovine kidney, and vacuum dried porcine stomach. As I said, this woman taking these nutritional supplements, died from CJD.
The particular batch of pills that was located, in which she was taking, was tested. From what I have heard, they came up negative, for the prion protein. But, in the same breath, they said their testing, may not have been strong enough to pick up the infectivity. Plus, she had been taking these type pills for years, so, could it have come from another batch?
CWD is just a small piece of a very big puzzle. I have seen while deer hunting, deer, squirrels and birds, eating from cattle feed troughs where they feed cattle, the high protein cattle by products, at least up until Aug. 4, 1997.
So why would it be so hard to believe that this is how they might become infected with a TSE. Or, even by potentially infected land. It's been well documented that it could be possible, from scrapie. Cats becoming infected with a TSE. Have you ever read the ingredients on the labels of cat and dog food? But, they do not put these tissues from these animals in pharmaceuticals, cosmetics, nutritional supplements, hGH, hPG, blood products, heart valves, and the many more products that come from bovine, ovine, or porcine tissues and organs. So, as I said, this CWD would be a small piece of a very big puzzle. But, it is here, and it most likely has killed. You see, greed is what caused this catastrophe, rendering and feeding practices. But, once Pandora's box was opened, the potential routes of infection became endless.
No BSE in the U.S.A.? I would not be so sure of that considering that since 1990;
Since 1990 the U.S. has raised 1,250,880,700 cattle;
Since 1990 the U.S. has ONLY checked 8,881 cattle brains for BSE, as of Oct. 4, 1999;
There are apprx. 100,000 DOWNER cattle annually in the U.S., that up until Aug. 4, 1997 went to the renders for feed;
Scrapie running rampant for years in the U.S., 950 infected FLOCKS, as of Aug. 1999;
Our feeding and rendering practices have mirrored that of the U.K. for years, some say it was worse. Everything from the downer cattle, to those scrapie infected sheep, to any roadkill, including the city police horse and the circus elephant went to the renders for feed and other products for consumption. Then they only implemented a partial feed ban on Aug. 4, 1997, but pigs, chickens, dogs, and cats, and humans were exempt from that ban. So they can still feed pigs and chickens those potentially TSE tainted by-products, and then they can still feed those by-products back to the cows. I believe it was Dr. Joe Gibbs, that said, the prion protein, can survive the digestinal track. So you have stopped nothing. It was proven in Oprah Winfrey's trial, that Cactus Cattle feeders, sent neurologically ill cattle, some with encephalopathy stamped on the dead slips, were picked up and sent to the renders, along with sheep carcasses. Speaking of autopsies, I have a stack of them, from CJD victims. You would be surprised of the number of them, who ate cow brains, elk brains, deer brains, or hog brains.
I believe all these TSE's are going to be related, and originally caused by the same greedy Industries, and they will be many. Not just the Renders, but you now see, that they are re-using medical devices that were meant for disposal. Some medical institutions do not follow proper auto- claving procedures (even Olympus has put out a medical warning on their endoscopes about CJD, and the fact you cannot properly clean these instruments from TSE's), and this is just one product. Another route of infection.
Regardless what the Federal Government in the U.S. says. It's here, I have seen it, and the longer they keep sweeping it under the rug and denying the fact that we have a serious problem, one that could surpass aids (not now, but in the years to come, due to the incubation period), they will be responsible for the continued spreading of this deadly disease.
It's their move, it's CHECK, but once CHECKMATE has been called, how many thousands or millions, will be at risk or infected or even dead. You can't play around with these TSE's. I cannot stress that enough. They are only looking at body bags, and the fact the count is so low. But, then you have to look at the fact it is not a reportable disease in most states, mis-diagnosis, no autopsies performed. The fact that their one-in-a- million theory is a crude survey done about 5 years ago, that's a joke, under the above circumstances. A bad joke indeed........
The truth will come, but how many more have to die such a hideous death. It's the Government's call, and they need to make a serious move, soon. This problem, potential epidemic, is not going away, by itself.
Terry S. Singeltary Sr.
P.O. Box
Bacliff, Texas 77518 USA
flounder@wt.net
Competing interests: No competing interests
February 14, 2001
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Terry S. Singeltary, Sr
Author Affiliations
JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214
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.
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Terry S. Singeltary, retired (medically), CJD WATCH
Submitted March 26, 2003
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?
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009
August 10, 2009
Greetings,
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. North America seems to have the most species with documented Transmissible Spongiform Encephalopathy's, most all of which have been rendered and fed back to food producing animals and to humans for years. If you look at the statistics, sporadic CJD seems to be rising in the USA, and has been, with atypical cases of the sCJD. I find deeply disturbing in the year of 2009, that Human Transmissible Spongiform Encephalopathy of any strain and or phenotype, of all age groups, and I stress all age groups, because human TSE's do not know age, and they do not know borders. someone 56 years old, that has a human TSE, that has surgery, can pass this TSE agent on i.e. friendly fire, and or passing it forward, and there have been documented nvCJD in a 74 year old. Remembering also that only sporadic CJD has been documented to transmit via iatrogenic routes, until recently with the 4 cases of blood related transmission, of which the origin is thought to be nvCJD donors. However most Iatrogenic CJD cases are nothing more than sporadic CJD, until the source is proven, then it becomes Iatrogenic. An oxymoron of sorts, because all sporadic CJD is, are multiple forms, or strains, or phenotypes of Creutzfeldt Jakob Disease, that the route and source and species have not been confirmed and or documented. When will the myth of the UKBSEnvCJD only theory be put to bed for good. This theory in my opinion, and the following there from, as the GOLD STANDARD, has done nothing more than help spread this agent around the globe. Politics and money have caused the terrible consequences to date, and the fact that TSEs are a slow incubating death, but a death that is 100% certain for those that are exposed and live long enough to go clinical. once clinical, there is no recourse, to date. But, while sub-clinical, how many can one exposed human infect? Can humans exposed to CWD and scrapie strains pass it forward as some form of sporadic CJD in the surgical and medical arenas? why must we wait decades and decades to prove this point, only to expose millions needlessly, only for the sake of the industries involved? would it not have been prudent from the beginning to just include all TSE's, and rule them out from there with transmission studies and change policies there from, as opposed to doing just the opposite? The science of TSE's have been nothing more than a political circus since the beginning, and for anyone to still believe in this one strain, one group of bovines, in one geographical location, with only one age group of human TSE i.e. nvCJD myth, for anyone to believe this today only enhances to spreading of these human and animal TSE's. This is exactly why we have been in this quagmire.
The ones that believe that there is a spontaneous CJD in 85%+ of all cases of human TSE, and the ones that do not believe that cattle can have this same phenomenon, are two of the same, the industry, and so goes the political science aspect of this tobacco and or asbestos scenario i.e. follow the money. I could go into all angles of this man made nightmare, the real facts and science, for instance, the continuing rendering technology and slow cooking with low temps that brewed this stew up, and the fact that THE USA HAD THIS TECHNOLOGY FIRST AND SHIPPED IT TO THE U.K. SOME 5 YEARS BEFORE THE U.S. STARTED USING THE SAME TECHNOLOGY, to save on fuel cost. This is what supposedly amplified the TSE agent via sheep scrapie, and spread via feed in the U.K. bovine, and other countries exporting the tainted product. BUT most everyone ignores this fact, and the fact that the U.S. has been recycling more TSE, from more species with TSEs, than any other country documented, but yet, it's all spontaneous, and the rise in sporadic CJD in the U.S. is a happenstance of bad luck ??? I respectfully disagree. To top that all off, the infamous BSE-FIREWALL that the USDA always brags about was nothing more than ink on paper, and I can prove this. YOU can ignore it, but this is FACT (see source, as late as 2007, in one recall alone, some 10,000,000 MILLION POUNDS OF BANNED MAD COW FEED WENT OUT INTO COMMERCE TO BE FED OUT, and most was never recovered. This was banned blood laced, meat and bone meal. 2006 was a banner year for banned mad cow protein going into commerce in the U.S. (see source of FDA feed ban warning letter below). I stress that the August 4, 1997 USA mad cow feed ban and this infamous BSE firewall, was nothing more than ink on paper, it was never enforceable.
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route. This would further have to be broken down to strain of species and then the route of transmission would further have to be broken down. Accumulation and Transmission are key to the threshold from sub- clinical to clinical disease, and key to all this, is to stop the amplification and transmission of this agent, the spreading of, no matter what strain. In my opinion, to continue with this myth that the U.K. strain of BSE one strain TSE in cows, and the nv/v CJD one strain TSE humans, and the one geographical location source i.e. U.K., and that all the rest of human TSE are just one single strain i.e. sporadic CJD, a happenstance of bad luck that just happens due to a twisted protein that just twisted the wrong way, IN 85%+ OF ALL HUMAN TSEs, when to date there are 6 different phenotypes of sCJD, and growing per Gambetti et al, and that no other animal TSE transmits to humans ??? With all due respect to all Scientist that believe this, I beg to differ. To continue with this masquerade will only continue to spread, expose, and kill, who knows how many more in the years and decades to come. ONE was enough for me, My Mom, hvCJD i.e. Heidenhain Variant CJD, DOD 12/14/97 confirmed, which is nothing more than another mans name added to CJD, like CJD itself, Jakob and Creutzfeldt, or Gerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE, named after another human. WE are only kidding ourselves with the current diagnostic criteria for human and animal TSE, especially differentiating between the nvCJD vs the sporadic CJD strains and then the GSS strains and also the FFI fatal familial insomnia strains or the ones that mimics one or the other of those TSE? Tissue infectivity and strain typing of the many variants of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ...
please see history, and the ever evolving TSE science to date ;
Saturday, June 13, 2009
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009
Singeltary 2000
BMJ 2000; 320 doi: https://doi.org/10.1136/bmj.320.7226.8/b (Published 01 January 2000) Cite this as: BMJ 2000;320:8
02 January 2000 Terry S Singeltary retired
Rapid Response:
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well...
In reading your short article about 'Scientist warn of CJD epidemic' news in brief Jan. 1, 2000. I find the findings in the PNAS old news, made famous again. Why is the U.S. still sitting on their butts, ignoring the facts? We have the beginning of a CJD epidemic in the U.S., and the U.S. Gov. is doing everything in it's power to conceal it.
The exact same recipe for B.S.E. existed in the U.S. for years and years. In reading over the Qualitative Analysis of BSE Risk Factors-1, this is a 25 page report by the USDA:APHIS:VS. It could have been done in one page. The first page, fourth paragraph says it all;
"Similarities exist in the two countries usage of continuous rendering technology and the lack of usage of solvents, however, large differences still remain with other risk factors which greatly reduce the potential risk at the national level."
Then, the next 24 pages tries to down-play the high risks of B.S.E. in the U.S., with nothing more than the cattle to sheep ratio count, and the geographical locations of herds and flocks. That's all the evidence they can come up with, in the next 24 pages.
Something else I find odd, page 16;
"In the United Kingdom there is much concern for a specific continuous rendering technology which uses lower temperatures and accounts for 25 percent of total output. This technology was _originally_ designed and imported from the United States. However, the specific application in the production process is _believed_ to be different in the two countries."
A few more factors to consider, page 15;
"Figure 26 compares animal protein production for the two countries. The calculations are based on slaughter numbers, fallen stock estimates, and product yield coefficients. This approach is used due to variation of up to 80 percent from different reported sources. At 3.6 million tons, the United States produces 8 times more animal rendered product than the United Kingdom."
"The risk of introducing the BSE agent through sheep meat and bone meal is more acute in both relative and absolute terms in the United Kingdom (Figures 27 and 28). Note that sheep meat and bone meal accounts for 14 percent, or 61 thousand tons, in the United Kingdom versus 0.6 percent or 22 thousand tons in the United States. For sheep greater than 1 year, this is less than one-tenth of one percent of the United States supply."
"The potential risk of amplification of the BSE agent through cattle meat and bone meal is much greater in the United States where it accounts for 59 percent of total product or almost 5 times more than the total amount of rendered product in the United Kingdom."
Considering, it would only take _one_ scrapie infected sheep to contaminate the feed. Considering Scrapie has run rampant in the U.S. for years, as of Aug. 1999, 950 scrapie infected flocks. Also, Considering only one quarter spoonful of scrapie infected material is lethal to a cow.
Considering all this, the sheep to cow ration is meaningless. As I said, it's 24 pages of B.S.e.
To be continued...
Terry S. Singeltary Sr. Bacliff, Texas USA
Competing interests: No competing interests
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
Volume 3, Number 8 01 August 2003
Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
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.
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.
Singeltary 2007
The Pathological Protein: Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases
by Philip Yam
''Answering critics like Terry Singeltary, who feels that the US undercounts CJD, Schonberger _conceded_ that the current surveillance system has errors but stated that most of the errors will be confined to the older population''...
Revisiting Sporadic CJD
It’s not hard to get Terry Singeltary going. “I have my conspiracy theories,” admitted the 49-year-old Texan.1 Singeltary is probably the nation’s most relentless consumer advocate when it comes to issues in prion diseases. He has helped families learn about the sickness and coordinated efforts with support groups such as CJD Voice and the CJD Foundation. He has also connected with others who are critical of the American way of handling the threat of prion diseases. Such critics include Consumers Union’s Michael Hansen, journalist John Stauber, and Thomas Pringle, who used to run the voluminous www.madcow.org Web site. These three lend their expertise to newspaper and magazine stories about prion diseases, and they usually argue that
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prions represent more of a threat than people realize, and that the government has responded poorly to the dangers because it is more concerned about protecting the beef industry than people’s health.
Singeltary has similar inclinations, but unlike these men, he doesn’t have the professional credentials behind him. He is an 11th-grade dropout, a machinist who retired because of a neck injury sustained at work. But you might not know that from the vast stores of information in his mind and on his hard drive. Over the years, he has provided unacknowledged help to reporters around the globe, passing on files to such big-time players as The New York Times, Newsweek, and USA Today. His networking with journalists, activists, and concerned citizens has helped medical authorities make contact with suspected CJD victims. He has kept scientists informed with his almost daily posting of news items and research abstracts on electronic newsgroups, including the bulletin board on www.vegsource.com and the BSE-listserv run out of the University of Karlsruhe, Germany. His combative, blunt, opinionated style sometimes borders on obsessive ranting that earns praise from some officials and researchers but infuriates others—especially when he repeats his conviction that “the government has lied to us, the feed industry has lied to us—all over a buck.” As evidence, Singeltary cites the USDA’s testing approach, which targets downer cows and examined 19,900 of them in 2002. To him, the USDA should test 1 million cattle, because the incidence of BSE may be as low as one in a million, as it was in some European countries. That the U.S. does not, he thinks, is a sign that the government is really not interested in finding mad cows because of fears of an economic disaster.
Singeltary got into the field of transmissible spongiform encephalopathy in 1997, just after his mother died of sporadic CJD. She had an especially aggressive version—the Heidenhain variant—that first causes the patient to go blind and then to deteriorate rapidly. She died just ten weeks after her symptoms began. Singeltary, who said he had watched his grandparents die of cancer, considered her death by CJD to be much, much worse: “It’s something you never forget.” Her uncontrollable muscle twitching became so bad “that it took three of us to hold her one time,” Singeltary recalled. “She did everything but levitate in bed and spin her head.” Doctors originally diagnosed Alzheimer’s disease, but a postmortem neuropathological exam demanded by Singeltary revealed the true nature of her death.
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Classifying a disease as “sporadic” is another way for doctors to say they don’t know the cause. Normal prion proteins just turn rogue in the brain for no apparent reason. The term “sporadic” is often particularly hard for the victims’ families to accept, especially when the patient was previously in robust health. Maybe it was something in the water, they wonder, or in the air, or something they ate—the same questions CJD researchers tried to answer decades ago. The names “sporadic CJD” and “variant CJD” also confuse the public and raise suspicions that U.S. authorities are hiding something when they say there have been no native variant CJD cases in the country.
Singeltary suspected an environmental cause in his mother’s demise—a feeling reinforced a year later when a neighbor died of sporadic CJD. For years, the neighbor had been taking nutritional supplements that contained cow brain extracts. Researchers from the National Institutes of Health collected samples of the supplement, Singeltary recounted, and inoculated suspensions into mice. The mice remained healthy—which only means that those supplement samples tested were prion-free.
Scientists have made several attempts during the past few decades to find a connection between sporadic CJD and the environment. Often, these studies take the form of asking family members about CJD victims—their diet, occupation, medical history, hobbies, pets, and so forth—and comparing them with non-CJD subjects. Such case-control CJD studies have produced some intriguing—and sometimes contradictory—results. In 1985, Carleton Gajdusek and his NIH colleagues reported a correlation between CJD and eating a lot of roast pork, ham, hot dogs, and lamb, as well as rare meats and raw oysters.2 Yet they also recognized that the findings were preliminary and that more studies were needed.
Following up, Robert Will of the U.K. National CJD Surveillance Unit and others pooled this data with those from two other case-control studies on CJD (one from Japan and one from the U.K.). In particular, they figured the so-called odds ratio—calculated by dividing the frequency of a possible factor in the patient group by the frequency of the factor in the control group. An odds ratio greater than 1 means that the factor may be significant. In their study, Will and his collaborators found an increase of CJD in people who have worked as health professionals (odds ratio of 1.5) and people who have had contact with cows
Laying Odds 225
(1.7) and sheep (1.6). Unfortunately, those connections were not statistically significant: The numbers of pooled patients (117) and control subjects (333) were so small that the researchers felt the odds ratios needed to reach 2.5 to 8 (depending on the assumptions) before they could be deemed statistically significant. The only statistically significant correlations they found were between CJD and a family history of either CJD (19.1) or other psychotic disease (9.9), although the latter might simply be correlated because psychotic disease may be an early symptom of undiagnosed CJD.3 In contrast with earlier findings, the team concluded that there was no association between sporadic CJD and the consumption of organ meats, including brains (0.6).
Although these case-control studies shed a certain amount of light on potential risk factors for CJD, it’s impossible to draw firm conclusions. Obtaining data that produces statistically meaningful results can be difficult because of the rarity of CJD and hence the shortage of subjects. Human memory is quite fragile, too, so patients’ families may not accurately recall the lifestyle and dietary habits of their loved ones over the course of a decade or more. Consequently, researchers must cope with data that probably contain significant biases. In a review paper on CJD, Joe Gibbs of the NIH and Richard T. Johnson of Johns Hopkins University concluded that “the absence of geographic differences in incidence is more convincing evidence against major dietary factors, since large populations eschew pork and some consume no meat or meat products.” A CJD study of lifelong vegetarians, they proposed, could produce some interesting data.4
The inconclusive results of case-control studies do not completely rule out the environment as a possible cause of CJD. “Dr. Prusiner’s theory does fit much of the data of spontaneous generation of [malformed] PrP somewhere in the brain,” Will remarked—that is, the idea that sporadic CJD just happens by itself falls within the realm of the prion theory. Still, “it’s very odd, if you look at all the forms of human prion diseases there are, all of them are transmissible in the laboratory and could be due to some sort of infectious agent.”5 One of the great difficulties, he explained, is that “given that this is a disease of an extraordinarily long incubation period, are we really confident that we can exclude childhood exposure that is transmitted from person to person, as people move around? It’s difficult to be sure about that.” There might a “carrier state” that leaves people healthy yet still able to
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infect others. If so, “you would never be able to identify what’s causing the spread of the disease,” concluded Will, who hasn’t stopped looking for a possible environmental link. He has some preliminary data based on studies that trace CJD victims’ lives well before the time symptoms began—up to 70 years; they suggest some degree of geographic clustering, but no obvious candidates for a source of infection.
A Case for Undercounting
The difficulty in establishing causal links in sporadic prion diseases—if there are any in the first place—underlines the importance of thorough surveillance. The U.K. has an active program, and when a victim of CJD is reported, one of Robert Will’s colleagues visits and questions the victim’s family. “No one has looked for CJD systematically in the U.S.,” the NIH’s Paul Brown noted. “Ever.”6 The U.S., through the Centers for Disease Control and Prevention, has generally maintained a more passive system, collecting information from death certificates from the National Center for Health Statistics. Because CJD is invariably fatal, mortality data is considered to be an effective means of tabulating cases. The CDC assessed the accuracy of such data by comparing the numbers with figures garnered through an active search in 1996: Teams covering five regions of the U.S. contacted the specialists involved and reviewed medical records for CJD cases between 1991 and 1995. Comparing the actively garnered data with the death certificate information showed that “we miss about 14 percent,” said CDC epidemiologist Lawrence Schonberger. “That’s improving. Doctors are becoming more knowledgeable,” thanks to increased scientific and media attention given to prion diseases.7
The active surveillance study of 1996, however, only looked at cases in which physicians attributed the deaths to CJD. Misdiagnosed patients or patients who never saw a neurologist were not tabulated— thus CJD may be grossly underreported. Many neurological ailments share symptoms, especially early on. According to various studies, autopsies have found that CJD is misdiagnosed as other ills, such as dementia or Alzheimer’s disease, 5 to 13 percent of the time. The CDC finds that around 50,000Americans die from Alzheimer’s each year
Laying Odds 227
(about 4 million have the disease, according to the Alzheimer’s Association). Therefore, one could argue that thousands of CJD cases are being missed. (On the flip side, CJD could be mistakenly diagnosed as Alzheimer’s disease or dementia, but the number of CJD patients is so small that they wouldn’t dramatically skew the statistics for other neurological ills.)
In part to address the issue of misdiagnosis, CJD families have asked the CDC to place the disease on the national list of officially notifiable illnesses, which tends to include more contagious conditions such as AIDS, tuberculosis, hepatitis, and viral forms of encephalitis. Currently, only some states impose this requirement. CDC officials have discounted the utility of such an approach, arguing that it would duplicate the mortality data, which is more accurate than early diagnoses of CJD, anyway. Moreover, mandatory reporting of CJD cases does not necessarily guarantee the end to missed cases.8
One clue suggests that the passive system is undercounting CJD in the U.S.: racial difference. The number of black CJD victims is about 38 percent that of white victims. Rather than sporadic CJD being a onein-a-million lottery, it’s more like one-in-2.5-million for AfricanAmericans. Access to medical care might be one reason. Schonberger recounted that the CDC had asked other countries with substantial black populations to submit CJD figures for comparison but found that the surveillance in those countries was inadequate. “We haven’t been able to find any comparable literature on this issue, so it’s still up in the air,” Schonberger said. On the other hand, Alzheimer’s disease is more common among black people than whites, with an estimated higher prevalence ranging from 14 percent to almost 100 percent, according to a February 2002 report by the Alzheimer’s Association. Are some black CJD cases being misdiagnosed as Alzheimer’s?
Answering critics like Terry Singeltary, who feels that the U.S. undercounts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population. As Schonberger pointed out, no doctor would misdiagnose a 30-year-old CJD patient as having Alzheimer’s. The average age of the first 100 variant CJD victims was 29; should the epidemiology of vCJD change—if older people start coming down with it—then there would be problems. “The adequacy of our overall CJD surveillance would be greatly reduced should the proportion of older individuals affected by variant CJD substantially increase,” Schonberger explained.9
SNIP...SEE FULL TEXT;
Singeltary Submission SEAC 2007
SEAC SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Minutes of the 99th meeting held on 14th December 2007 Singeltary Submission
This was 22 years to the day Mom died from the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. hvCJD, when i made this submission to SEAC and this was their reply to my questions of concern about cjd in the USA, my how things have changed...terry
SEAC SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Minutes of the 99th meeting held on 14th December 2007
ITEM 8 – PUBLIC QUESTION AND ANSWER SESSION 40. The Chair explained that the purpose of the question and answer session was to give members of the public an opportunity to ask questions related to the work of SEAC. Mr Terry Singeltary (Texas, USA) had submitted a question prior to the meeting, asking: “With the Nor-98 now documented in five different states so far in the USA in 2007, and with the two atypical BSE H-base cases in Texas and Alabama, with both scrapie and chronic wasting disease (CWD) running rampant in the USA, is there any concern from SEAC with the rise of sporadic CJD in the USA from ''unknown phenotype'', and what concerns if any, in relations to blood donations, surgery, optical, and dental treatment, do you have with these unknown atypical phenotypes in both humans and animals in the USA? Does it concern SEAC, or is it of no concern to SEAC? Should it concern USA animal and human health officials?”
41. A member considered that this question appeared to be primarily related to possible links between animal and human TSEs in the USA. There is no evidence that sCJD is increasing in the USA and no evidence of any direct link between TSEs and CJD in the USA. Current evidence does not suggest that CWD is a significant risk to human health. There are unpublished data from a case of human TSE in the USA that are suggestive of an apparently novel form of prion disease with distinct molecular characteristics. However, it is unclear whether the case had been further characterised, if it could be linked to animal TSEs or if other similar cases had been found in the USA or elsewhere. In relation to the possible public health implications of atypical scrapie, H-type BSE and CWD, research was being conducted to investigate possible links and surveillance was in place to detect any changes in human TSEs. Although possible links between these diseases and human TSEs are of concern and require research, there is no evidence to suggest immediate public health action is warranted. The possible human health risks from classical scrapie had been discussed earlier in the meeting. Members noted that there are effective channels of discussion and collaboration on research between USA and European groups. Members agreed it is important to keep a watching brief on new developments on TSEs.
Alzheimer's disease, iatrogenic transmission, what if?
let's not forget the elephant in the room. curing Alzheimer's would be a great and wonderful thing, but for starters, why not start with the obvious, lets prove the cause or causes, and then start to stop that. think iatrogenic, friendly fire, or the pass it forward mode of transmission. think medical, surgical, dental, tissue, blood, related transmission. think transmissible spongiform encephalopathy aka tse prion disease aka mad cow type disease...
Commentary: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
*** Singeltary comment PLoS ***
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Background
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease have both been around a long time, and was discovered in or around the same time frame, early 1900’s. Both diseases are incurable and debilitating brain disease, that are in the end, 100% fatal, with the incubation/clinical period of the Alzheimer’s disease being longer (most of the time) than the TSE prion disease. Symptoms are very similar, and pathology is very similar.
Methods
Through years of research, as a layperson, of peer review journals, transmission studies, and observations of loved ones and friends that have died from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant Creutzfelt Jakob Disease CJD.
Results
I propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation disease, and that Alzheimer’s is Transmissible, and is a threat to the public via the many Iatrogenic routes and sources. It was said long ago that the only thing that disputes this, is Alzheimer’s disease transmissibility, or the lack of. The likelihood of many victims of Alzheimer’s disease from the many different Iatrogenic routes and modes of transmission as with the TSE prion disease.
Conclusions
There should be a Global Congressional Science round table event set up immediately to address these concerns from the many potential routes and sources of the TSE prion disease, including Alzheimer’s disease, and a emergency global doctrine put into effect to help combat the spread of Alzheimer’s disease via the medical, surgical, dental, tissue, and blood arena’s. All human and animal TSE prion disease, including Alzheimer’s should be made reportable in every state, and Internationally, WITH NO age restrictions. Until a proven method of decontamination and autoclaving is proven, and put forth in use universally, in all hospitals and medical, surgical arena’s, or the TSE prion agent will continue to spread. IF we wait until science and corporate politicians wait until politics lets science _prove_ this once and for all, and set forth regulations there from, we will all be exposed to the TSE Prion agents, if that has not happened already.
MONDAY, APRIL 24, 2023
2023 CDC REPORTS CJD TSE Prion 5 cases per million in persons 55 years of age or older
WEDNESDAY, FEBRUARY 8, 2023
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Creutzfeldt Jacob Disease CJD TSE Prion December 2022 Annual Update
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WAHIS, WOAH, OIE, United States of America Bovine spongiform encephalopathy Immediate notification
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Tennessee State Veterinarian Alerts Cattle Owners to Disease Detection Mad Cow atypical L-Type BSE
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BSE TSE Prion MAD COW TESTING IN THE USA COMPARED TO OTHER COUNTRIES?
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World Organisation for Animal Health 90th General Session of the World Assembly of Delegates BSE TSE Prion 2023
BSE--U.S. 50 STATE CONFERENCE CALL Jan. 9, 2001
Date: Tue, 9 Jan 2001 16:49:00 -0800
From: "Terry S. Singeltary Sr."
Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
Terry S. Singeltary Sr.
posted by Terry S. Singeltary Sr. at
11:54 AM
