Thursday, May 17, 2012

Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment

Volume 18, Number 6—June 2012


CME ACTIVITY


Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment




Paul Brown , Jean-Philippe Brandel, Takeshi Sato, Yosikazu Nakamura, Jan MacKenzie, Robert G. Will, Anna Ladogana, Maurizio Pocchiari, Ellen W. Leschek, and Lawrence B. Schonberger Author affiliations: Centre à l’Energie Atomique, Fontenay-aux-Roses, France (P. Brown); Institut National de la Santé et de la Recherche Médicale, Paris, France (J.-P. Brandel); Nanohana Clinic, Tokyo, Japan (T. Sato); Jichi Medical University, Yakushiji, Japan (Y. Nakamura); Western General Hospital, Edinburgh, Scotland, UK (J. MacKenzie, R.G. Will); Istituto Superiore de Sanità, Rome, Italy (A. Ladogana, M. Pocchiari); National Institutes of Health, Bethesda, Maryland, USA (E.W. Leschek); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (L.B. Schonberger)




Abstract


The era of iatrogenic Creutzfeldt-Jakob disease (CJD) has nearly closed; only occasional cases with exceptionally long incubation periods are still appearing. The principal sources of these outbreaks are contaminated growth hormone (226 cases) and dura mater grafts (228 cases) derived from human cadavers with undiagnosed CJD infections; a small number of additional cases are caused by neurosurgical instrument contamination, corneal grafts, gonadotrophic hormone, and secondary infection with variant CJD transmitted by transfusion of blood products. No new sources of disease have been identified, and current practices, which combine improved recognition of potentially infected persons with new disinfection methods for fragile surgical instruments and biological products, should continue to minimize the risk for iatrogenic disease until a blood screening test for the detection of preclinical infection is validated for human use.


The first case of what would eventually become a major outbreak of iatrogenic Creutzfeldt-Jakob disease (CJD) was reported in 1974; the patient had received a corneal transplant from an infected cadaver (1). In the years that followed, other sources of infection were identified: stereotactic electroencephalogram electrodes, neurosurgical instruments, cadaveric dura mater and pituitary glands, and, most recently, secondary variant CJD (vCJD) blood products. The ensemble of iatrogenic cases, including a bibliography of primary references, was last reviewed in 2006 (2). Today, after nearly 40 years of surveillance, the chronology and essential characteristics of iatrogenic CJD have been finalized, and the purpose of this article is to present these data along with a few brief comments about factors that determined the risk for infection and how future risks might be foreseen and avoided.




By far the most common sources of iatrogenic disease were human cadavers from which pituitary hormones and dura mater grafts were obtained (Table 1; Figure); the other major variety of environmentally acquired disease is vCJD. The incidence curves of human growth hormone–associated and dura mater–associated CJD are almost superimposable; a broad peak occurred in the mid-to-late 1990s, just ahead of the sharper peak incidence of vCJD in the United Kingdom at the turn of the century. The incidence in other countries peaked a few years later, in 2004, as a result of the delayed appearance of bovine spongiform encephalopathy in those countries.


The long incubation periods—years to decades—of these low-dose infections pose a particularly difficult problem for public health officials, whose recommendations may diminish the number of new cases but are impotent when it comes to preventing cases in already-infected persons in the preclinical phase of disease. It is worth remembering that the early recognition of iatrogenic sources of CJD was entirely because of a few remarkably astute neurologists, neurosurgeons, and, astonishingly, a pediatric endocrinologist who pursued the unlikely (and unpopular) diagnosis of CJD in a growth hormone recipient (3). It is true that some of these connections had the benefit of comparatively short intervals between the infecting events and the onset of CJD. It is especially fortunate from the standpoint of early recognition of the dura mater association that the interval of 19 months between the operation and onset of symptoms in the first case-patient was among the shortest on record for this form of iatrogenic CJD (Table 2).






Human Growth Hormone


The current worldwide total of growth hormone–associated cases of CJD is 226. Most cases occurred in France (119 cases/1,880 recipients; attack rate 6.3%), the United Kingdom (65 cases/1,800 recipients; attack rate 3.6%), and the United States (29 cases/7,700 recipients; attack rate 0.4%).






In France, further epidemiologic observations have revealed that all 119 cases occurred within a 1,170-patient cohort receiving treatment during a 20-month period, from December 1983 through July 1985, when there seems to have been substantial contamination resulting from sourcing and processing deficiencies. According to these numbers, the attack rate for the at-risk cohort in France increases to 10.2%. No new case has been identified since 2008. In the United Kingdom, no cohort pattern is evident, and cases continue to occur at an average rate of about 2 per year (only 1 in 2011). In the United States, CJD has not occurred in any patient who started treatment after 1977, when a highly selective column chromatography step was introduced into the purification protocol. Since 2003, only 2 new cases have been identified (1 in 2007 and 1 in 2009). An estimated ≈2,700 patients received treatment before 1977, so the attack rate in the United States for this at-risk cohort increases to 1.1% (4). The revised attack rates therefore become 10.2% in France, 3.6% in the United Kingdom, and 1.1% in the United States.


The methionine (M)/valine polymorphism at codon 129 of the PRNP gene has been examined in populations with and without CJD in many countries; results have varied (Table 3). Overall, it is clear that the M allele bestows substantial susceptibility to the sporadic and the iatrogenic forms of CJD; in consequence, the proportion of persons with MM homozygous genotype is overrepresented in both categories of disease (the sole exception occurred in UK growth hormone recipients, which led to speculation that a different strain of the pathogenic agent might have been disseminated) (10). It is also clear that, as a group, persons with heterozygous genotype had longer incubation periods than did those with homozygous genotype, particularly in France. Notwithstanding this statistical conclusion, it is noteworthy that several persons with MM homozygous genotype had incubation periods >30 years, including a patient with recently diagnosed CJD, whose incubation period was 42 years, the current world record for any type of iatrogenic disease.






Incubation periods for the total case population (not just those examined for the codon 129 genotype) ranged from 5 to 42 years (mean 17 years), based on the interval between the midpoint date of what was almost always a multiyear period of treatment and the onset of CJD symptoms; the actual date of infection is impossible to determine. Mean incubation periods for cases in the United States and New Zealand (patients received hormone made in the United States) were 22 and 26 years; United Kingdom, 20 years; and France, 13 years. The shorter incubation periods in France could have resulted partly from the narrower limit for the date of infection in France and are in accord with the mean incubation period of 13.5 years in the 4 gonadotropin recipients from Australia, for whom there is an even more precise date of infection. However, a greater contribution probably came from different infectious doses received by patients in the different countries. Among all patients, the clinical features were distinctive in that, unlike sporadic CJD, signs and symptoms almost never included dementia, which, if it occurred at all, was typically a late component of the clinical course.






Dura Mater




The worldwide tally of dura mater–associated cases is 228, and new cases still continue to occur here and there, the most recent being individual cases in Austria, South Korea, and the Netherlands in 2011. If the pharmaceutical industry (in contrast to government-sponsored laboratories) comes away from the growth hormone story with an almost untainted record—only 1 case has been attributed to industrially prepared hormone (11)—the same cannot be said about the private sector producing dura mater grafts. The source of almost all infections was a manufacturer in Germany, B. Braun Melsungen AG, which has a worldwide distribution network, and the incidence of CJD appears to have more or less paralleled the frequency with which this source of dura mater was used. In Japan, it is estimated that as many as 20,000 patches may have been used each year, and the 142 cases in that country constitute two thirds of the global total. Nevertheless, the overall attack rate in the at-risk patient population in Japan is <0.03%. For the entire (worldwide) group of dura mater–recipient patients, incubation periods ranged from 1.3 to 30 years (mean 12 years), and, except in Japan, the clinical and neuropathologic features were similar to those of sporadic CJD. In Japan, approximately one third of the cases had atypical features (slow progression, noncharacteristic electroencephalogram tracings, plaque deposition, and an atypical prion protein molecular signature on Western blots), which suggested the possibility of 2 different strains of infecting agent (12,13). One patient had florid plaques and a pulvinar sign on magnetic resonance imaging, mimicking vCJD (5).


Evaluation of the influence of the codon 129 genotype is complicated by the fact that the population in Japan, among whom most cases occurred, has a high frequency of the M allele (>90%), which dominated sporadic and dura mater–associated forms of CJD (Table 3) (6–9,14,15). Among the cases in persons not from Japan, the distribution of genotypes approximated that found among patients with sporadic CJD, and, as with growth hormone–associated cases, incubation periods were somewhat longer for persons with heterozygous than with homozygous genotypes.






Current Prevention Strategies




The best way to abolish secondary iatrogenic infections is, obviously, to prevent primary infections, but without a test to identify infected but asymptomatic persons, we cannot entirely eliminate the risk inherent in human-to-human tissue transfer. We are therefore obliged to rely on the default strategies of 1) identification and donor deferral of persons at higher than normal risk for CJD development and 2) inclusion of prion-reduction steps in the sterilization of penetrating instruments and the processing of therapeutic tissues and fluids.






Delineation of high-risk categories initially focused on precisely those groups of persons who were exposed to the known sources of iatrogenic disease: recipients of cadaveric dura mater grafts or pituitary-derived hormones. When vCJD started to occur, restrictions were also placed on donor time of residence in the most heavily infected regions—the United Kingdom and, to a lesser extent, continental Europe—and embargoes were placed on the importation of biological products from these regions. These deferral and import restrictions remain in place today and need some thoughtful reevaluation in view of the near extinction of all such sources of iatrogenic CJD. In the United States, there have been only 4 cases of dura mater–associated disease (the most recent in 2005) and no case of growth hormone–associated CJD for anyone who began treatment after 1977.






On the other hand, the possibility of iatrogenic infection resulting from transfer of tissues or fluids from persons who have contracted a prion disease from animals has not disappeared with the abating epidemics of bovine spongiform encephalopathy and vCJD. A few persons who may be experiencing a long incubation phase of vCJD still pose an obvious danger in the United Kingdom, but an underappreciated potential danger lies in 2 other animal diseases: scrapie and chronic wasting disease (CWD). Although scrapie-infected sheep tissues have been consumed for long enough (hundreds of years) to be considered harmless for humans, the same cannot be said about the atypical strains of scrapie that are beginning to displace the typical strains and with which we do not yet have enough experience to evaluate human pathogenicity. Similarly, we cannot declare with certainty that CWD poses no threat to humans, and CWD is continuing its unchecked spread across the United States and Canada with no guarantee that it will not become globally distributed in the years to come. One hunter has already put a group of unwitting persons at risk for infection by donating a deer, later found to have CWD, for consumption at a rural banquet in New York State (16); more such exposures are likely to occur as CWD continues its geographic expansion.








Future Prevention Strategies




The issue of reducing risk by taking steps to inactivate prions is always a work in progress as new therapeutic products come into production and new methods to inactivate prions are discovered. The tried-and-true laboratory method of prion sterilization (1-hour exposures to either undiluted bleach or 1 N sodium hydroxide followed by steam autoclaving at 3 atmospheres pressure for 20 minutes) is applicable only to nonfragile instruments and not at all to living tissues. The surprising resistance of dura mater to 0.1 N sodium hydroxide (17) and of growth hormone to 6 M urea (18) led to their incorporation into processing protocols before being replaced by nondural tissue or synthetic patches and recombinant hormone. To reduce infectivity, blood, blood products, and other fluids can be subjected to nanofiltration and prion-affinity ligands (19–22), which should also be applicable to other biological products, for example, vaccine and stem cell cultures, should they be susceptible to infection (23). Fragile instruments such as endoscopes and electrodes remain a challenge, but new and gentler methods— alkaline cleaning solutions, phenolics, and gaseous hydrogen peroxide—have proven harmless to instruments and give a high, if not always complete, degree of prion inactivation (24–26).






The ongoing refinement of a quaking-induced conversion detection of the misfolded prion protein holds the best prospect of evolving into a sensitive and practical tool, but it has yet to be validated in blind testing of plasma from symptomatic patients or in presymptomatic persons, even more rigorous but necessary (27,28). It may be necessary to use scrapie-infected animals for presymptomatic validation because only 1 group of humans could furnish appropriate samples—asymptomatic carriers of CJD-inducing mutations—and putting together and testing a reasonable number of such samples will take years to accomplish.






The total numbers of cases for the 2 major causes of iatrogenic CJD during the past 40 years (226 growth hormone cases and 228 dura mater cases) are amazingly close and are likely to remain so after the few additional long-incubating cases finally surface in the next few years. The combination of appropriate blood donor deferrals and the incorporation of tissue, fluid, and instrument infectivity–reduction steps should continue to hold the sources of potential iatrogenic disease to a minimum until such time as a practical screening test for inapparent infection is validated for human use.






Dr Brown spent his career at the National Institutes of Health in the Laboratory of Central Nervous System Studies conducting research on the transmissible spongiform encephalopathies, especially with respect to epidemiology, iatrogenic CJD, disinfection, and blood infectivity. He currently chairs a scientific advisory committee for the Laboratoire Français du Fractionnement et des Biotechnologies in Les Ulis, France, and advises the Centre à l’Energie Atomique in Fontenay-aux-Roses, France.






Acknowledgment




Our profound thanks go to the physicians responsible for the earliest identification of iatrogenic CJD infections and to the multitude of unsung persons in many countries around the world who have worked diligently and continuously to keep track of its global incidence.






References




Duffy P, Wolf J, Collins G, DeVoe AB, Streeten B, Cowen D. Letter: possible person-to-person transmission of Creutzfeldt-Jakob disease. N Engl J Med. 1974;290:692–3. DOIPubMed Brown P, Brandel J-P, Preece M, Sato T. Iatrogenic Creutzfeldt-Jakob disease: the waning of an era. Neurology. 2006;67:389–93. DOIPubMed Brown P. Human growth hormone therapy and Creutzfeldt-Jakob disease: a drama in three acts. Pediatrics. 1988;81:85–92.PubMed Abrams JY, Schonberger LB, Belay ED, Maddox RA, Leschek EW, Mills JL, Lower risk of Creutzfeldt-Jakob disease in pituitary growth hormone recipients initiating treatment after 1977. J Clin Endocrinol Metab. 2011;96:E1666–9. DOIPubMed Wakisaka Y, Santa N, Doh-ura K, Kitamoto T, Ibayashi S, Iida M, Increased asymmetric pulvinar magnetic resonance imaging signals in Creutzfeldt-Jakob disease with florid plaques following a cadaveric dura mater graft. Neuropathology. 2006;26:82–8. DOIPubMed Soldevila M, Calafell F, Andrès AM, Yagüe J, Helgason A, Stefánsson K, Prion susceptibility and protective alleles exhibit marked geographic differences. Hum Mutat. 2003;22:104–5. DOIPubMed Nurmi MH, Bishop M, Strain L, Brett F, McGuigan C, Hutchison M, The normal population distribution of PRNP codon 129 polymorphism. Acta Neurol Scand. 2003;108:374–8. DOIPubMed Mercier G, Diéterlen F, Lucotte G. Population distribution of the methionine allele at the PRNP codon 129 polymorphism in Europe and the Middle East. Hum Biol. 2008;80:181–90. DOIPubMed Doh-ura K, Kitamoto T, Sakaki Y, Taateishi J. CJD discrepancy. Nature. 1991;353:801–2. DOIPubMed Brandel J-P, Preece M, Brown P, Croes E, Laplanche J-L, Agid Y, Distribution of codon 129 genotype in human growth hormone–treated CJD patients in France and the UK. Lancet. 2003;362:128–30. DOIPubMed Furtner M, Gelpi E, Kiechl S, Knoflach M, Zangerl A, Gotwald T, Iatrogenic Creutzfeldt-Jakob disease 22 years after human growth hormone therapy: clinical and radiological features. J Neurol Neurosurg Psychiatry. 2008;79:229–31. DOIPubMed Noguchi-Shinohara M, Hamaguchi T, Kitamoto T, Sato T, Nakamura Y, Mizusawa H, Clinical features and diagnosis of dura mater graft–associated Creutzfeldt-Jakob disease. Neurology. 2007;69:360–7. DOIPubMed Yamada M, Noguchi-Shinohara M, Hamaguchi T, Nozaki I, Kitamoto T, Sato T, Dura mater graft–associated Creutzfeldt-Jakob disease in Japan: clinicopathological and molecular characterization of the two distinct subtypes. Neuropathology. 2009;29:609–18. DOIPubMed Nozaki I, Hamaguchi T, Sanjo N, Noguchi-Shinohara M, Sakai K, Nakamura Y, Prospective 10-year surveillance of human prion diseases in Japan. Brain. 2010;133:3043–57. DOIPubMed Ladogana A, Puopolo M, Croes EA, Budka H, Jarius C, Collins S, Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada. Neurology. 2005;64:1586–91. DOIPubMed Garruto RM, Reiber C, Alfonso MP, Gastrich H, Needham K, Sunderman S, Risk behaviors in a rural community with a known point-source exposure to chronic wasting disease. Environ Health. 2008;7:31. DOIPubMed Diringer H, Braig HR. Infectivity of unconventional viruses in dura mater. Lancet. 1989;1:439–40. DOIPubMed Pocchiari M, Peano S, Conz A, Eshkol A, Maillard F, Brown P, Combination ultrafiltration and 6 M urea treatment of human growth hormone effectively minimizes risk from potential Creutzfeldt-Jakob disease virus contamination. Horm Res. 1991;35:161–6. DOIPubMed Yunoki M, Tanaka H, Urayama T, Hattori S, Ohtani M, Ohkubo Y, Prion removal by nanofiltraion under different experimental conditions. Biologicals. 2008;36:27–36. DOIPubMed Cardone F, Simoneau S, Arzel A, Puopolo M, Berardi VA, Abdel-Haq H, Comparison of nanofiltration efficacy in reducing infectivity of centrifuged versus ultracentrifuged 263K scrapie-infected brain homogenates in “spiked” albumin solutions. Transfusion. 2011. Epub ahead of print. DOIPubMed Gregori L, Gurgel PV, Lathrop JT, Edwardson P, Lambert BC, Carbonell RG, Reduction in infectivity of endogenous transmissible spongiform encephalopathies present in blood by adsorption to selective affinity resins. Lancet. 2006;368:2226–30. DOIPubMed Heger A, Bailey A, Neisser-Svae A, Ertl M, Römisch J, Svae TE. Removal of prion infectivity by affinity ligand chromatography during OctaplasLG manufacturing—results from animal bioassay studies. Vox Sang. 2011. Epub ahead of print. DOIPubMed Piccardo P, Cervenakova L, Vasilyeva I, Yakovleva O, Bacik I, Cervenak J, Candidate cell substrates, vaccine production, and transmissible spongiform encephalopathies. Emerg Infect Dis. 2011;17:2262–9. DOIPubMed Fichet G, Comoy E, Duval C, Antioga K, Dehen C, Charbonnier A, Novel methods for disinfection of prion-contaminated medical devices. Lancet. 2004;364:521–6. DOIPubMed Fichet G, Antioga K, Comoy E, Deslys JP, McDonnell G. Prion inactivation using a new gaseous hydrogen peroxide sterilization process. J Hosp Infect. 2007;67:278–86. DOIPubMed Fichet G, Harrison J, McDonnell G. Reduction of risk of prion transmission on surgical devices with effective cleaning processes. Zentr Steril. 2007;15:418–37. Orrú CD, Wilham JM, Raymond LD, Kuhn F, Schroeder B, Raeber AJ, Prion disease blood test using immunoprecipitation and improved quaking-induced conversion. MBiol. 2011;3:e00078-11 [cited 2012 Mar 31]. http://mbio.asm.org/content/2/3/e00078-11.full Orrú CD, Wilham JM, Vascellari S, Hughson AG, Caughey B. New generation QuIC assays for prion seeding activity. Prion. 2012;6. Epub ahead of print.


Figure


Figure. . . . Annual incidence of variant Creutzfeldt-Jakob disease (vCJD) caused by ingestion of meat products contaminated with bovine spongiform encephalopathy agent (A) and iatrogenic CJD caused by contaminated dura...


Tables


Table 1. Global distribution of cases of iatrogenic Creutzfeldt-Jakob disease


Table 2. Incubation periods and clinical presentations of iatrogenic Creutzfeldt-Jakob disease, according to source of infection


Table 3. Comparison of PRNP codon 129 genotype frequencies and incubation periods in growth hormone– and dura mater–associated cases of iatrogenic CJD


Suggested citation for this article: Brown P, Brandel J-P, Sato T, Nakamura Y, MacKenzie J, Will RG, et al. Iatrogenic Creutzfeldt-Jakob disease, final assessment. Emerg Infect Dis [serial on the Internet]. 2012 Jun [date cited]. http://dx.doi.org/10.3201/eid1806.120116


DOI: 10.3201/eid1806.120116






Volume 18, Number 6—June 2012 CME ACTIVITY Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment MEDSCAPE CME Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit.


This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and Emerging Infectious Diseases. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians.


Medscape, LLC designates this Journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.


All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at www.medscape.org/journal/eid; (4) view/print certificate.






Release date: May 16, 2012; Expiration date: May 16, 2013






Learning Objectives


Upon completion of this activity, participants will be able to:




• Distinguish the principal sources of iatrogenic CJD




• Identify countries with the highest rates of documented CJD




• Analyze the clinical presentation of iatrogenic CJD




• Assess new threats which might promote higher rates of CJD.




CME Editor


P. Lynne Stockton, Technical Writer/Editor, Emerging Infectious Diseases. Disclosure: P. Lynne Stockton has disclosed no relevant financial relationships.




CME AUTHOR


Charles P. Vega, MD, Health Sciences Clinical Professor; Residency Director, Department of Family Medicine, University of California, Irvine. Disclosure: Charles P. Vega, MD, has disclosed no relevant financial relationships.




AUTHORS


Disclosures: Paul Brown; Jean-Philippe Brandel; Takeshi Sato, MD; Yosikazu Nakamura, MD, MPH, FFPH; Jan MacKenzie; Anna Ladogana; Ellen W. Leschek, MD; and Lawrence B. Schonberger, MD, MPH, have disclosed no relevant financial relationships. Robert G. Will, FRCP, has disclosed the following relevant financial relationships: served as an advisor or consultant for LFB, Farring. Maurizio Pocchiari, MD, has disclosed the following relevant financial relationships: served as an advisor or consultant for LFB, Farring.










I hope and pray that Paul Brown et al rosey outlook is correct, and the end of iatrogenic Creutzfeldt Jakob Disease is truly over, bbut, I have my doubts. ...TSS






April 12, 2012


Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to 2010


Eurosurveillance,


Volume 17, Issue 15, 12


April 2012


Research articles








Sunday, May 6, 2012


Bovine Spongiform Encephalopathy Mad Cow Disease, BSE May 2, 2012 IOWA State University OIE








Friday, May 11, 2012


Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits


In addition, the present data will support risk assessments in some peripheral tissues derived from cattle affected with H-type BSE.








SPONTANEOUS ??? NOT...




How the California cow got the disease remains unknown. Government officials expressed confidence that contaminated food was not the source, saying the animal had atypical L-type BSE, a rare variant not generally associated with an animal consuming infected feed.




However, a BSE expert said that consumption of infected material is the only known way that cattle get the disease under natural conditons. “In view of what we know about BSE after almost 20 years experience, contaminated feed has been the source of the epidemic,” said Paul Brown, a scientist retired from the National Institute of Neurological Diseases and Stroke.




BSE is not caused by a microbe. It is caused by the misfolding of the so-called “prion protein” that is a normal constituent of brain and other tissues. If a diseased version of the protein enters the brain somehow, it can slowly cause all the normal versions to become misfolded. It is possible the disease could arise spontaneously, though such an event has never been recorded, Brown said.










Proposal ID: 29403




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 disease, and it’s variants, in many cases are merely names of the people that first discovered them. 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 than the TSE prion disease. Symptoms are very similar, and pathology is very similar. 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. today, there is enough documented science (some confidential), that shows that indeed Alzheimer’s is transmissible. The risk factor for friendly fire, and or the pass-it-forward mode i.e. Iatrogenic transmission is a real threat, and one that needs to be addressed immediately.




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




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. TSE prion disease survives ashing to 600 degrees celsius, that’s around 1112 degrees farenheit. you cannot cook the TSE prion disease out of meat. you can take the ash and mix it with saline and inject that ash into a mouse, and the mouse will go down with TSE. Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production as well. the TSE prion agent also survives Simulated Wastewater Treatment Processes. IN fact, you should also know that the TSE Prion agent will survive in the environment for years, if not decades. you can bury it and it will not go away. TSE prion agent is capable of infected your water table i.e. Detection of protease-resistant cervid prion protein in water from a CWD-endemic area. it’s not your ordinary pathogen you can just cook it out and be done with. that’s what’s so worrisome about Iatrogenic mode of transmission, a simple autoclave will not kill this TSE prion agent.




Conclusions




There should be a Global Congressional Science round table event (one of scientist and doctors et al only, NO CORPORATE, POLITICIANS ALLOWED) 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 let 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. what’s the use of science progressing human life to the century mark, if your brain does not work?








Wednesday, May 16, 2012


Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?


Proposal ID: 29403












Friday, February 10, 2012


Creutzfeldt-Jakob disease (CJD) biannual update (2012/1) potential iatrogenic (healthcare-acquired) exposure to CJD, and on the National Anonymous Tonsil Archive






Thursday, December 29, 2011


Aerosols An underestimated vehicle for transmission of prion diseases?


PRION www.landesbioscience.com


please see more on Aerosols and TSE prion disease here ;






Saturday, February 12, 2011


Another Pathologists dies from CJD, another potential occupational death ?


another happenstance of bad luck, a spontaneous event from nothing, or friendly fire ???






Tuesday, December 14, 2010


Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings part 4, Annex A1, Annex J,


UPDATE DECEMBER 2010






Tuesday, September 14, 2010


Transmissible Spongiform Encephalopathies Advisory Committee; Notice of Meeting October 28 and 29, 2010 (COMMENT SUBMISSION)








Thursday, September 02, 2010


NEUROSURGERY AND CREUTZFELDT-JAKOB DISEASE Health Law, Ethics, and Human Rights The Disclosure Dilemma








Thursday, August 12, 2010


USA Blood products, collected from a donor who was at risk for vCJD, were distributed July-August 2010








Sunday, August 01, 2010




Blood product, collected from a donors possibly at increased risk for vCJD only, was distributed USA JULY 2010
















Thursday, July 08, 2010


Nosocomial transmission of sporadic Creutzfeldt–Jakob disease: results from a risk-based assessment of surgical interventions Public release date: 8-Jul-2010






Thursday, July 08, 2010


GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010






Wednesday, June 02, 2010


CJD Annex H UPDATE AFTER DEATH PRECAUTIONS Published: 2 June 2003 Updated: May 2010








Tuesday, May 11, 2010


Current risk of iatrogenic Creutzfeld–Jakob disease in the UK: efficacy of available cleaning chemistries and reusability of neurosurgical instruments








Tuesday, May 04, 2010


Review of the Human Pituitary Trust Account and CJD Issue 20 January 2010








Tuesday, March 16, 2010


Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Part 4 REVISED FEB. 2010








Monday, August 17, 2009


Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection: Annex J,K, AND D Published: 2009








Monday, July 20, 2009


Pre-surgical risk assessment for variant Creutzfeldt-Jakob disease (vCJD) risk in neurosurgery and eye surgery units








Friday, July 17, 2009


Revision to pre-surgical assessment of risk for vCJD in neurosurgery and eye surgery units Volume 3 No 28; 17 July 2009








Sunday, May 10, 2009


Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)








Thursday, January 29, 2009


Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999-2008 (WARNING TO Neurosurgeons and Ophthalmologists) Volume 15, Number 2-February 2009 Research








Wednesday, August 20, 2008


Tonometer disinfection practice in the United Kingdom: A national survey








Tuesday, August 12, 2008


Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)








Monday, December 31, 2007


Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in Endodontic Practice in Absence of Adequate Prion Inactivation










Subject: CJD: update for dental staff


Date: November 12, 2006 at 3:25 pm PST


1: Dent Update. 2006 Oct;33(8):454-6, 458-60.


CJD: update for dental staff.








Saturday, January 16, 2010


Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al


Evidence For CJD/TSE Transmission Via Endoscopes


From Terry S. Singletary, Sr flounder@wt.net 1-24-3








2011 TO 2012 UPDATE




Saturday, December 3, 2011


Candidate Cell Substrates, Vaccine Production, and Transmissible Spongiform Encephalopathies


Volume 17, Number 12—December 2011








Sunday, June 26, 2011


Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque








Monday, February 7, 2011


FDA’s Currently-Recommended Policies to Reduce the Possible Risk of Transmission of CJD and vCJD by Blood and Blood Products 2011 ???






Saturday, March 5, 2011


MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA








Sunday, February 12, 2012


National Prion Disease Pathology Surveillance Center Cases Examined1 (August 19, 2011) including Texas








Terry S. Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis


















full text with source references ;










Subject: Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products APHIS-2008-0010-0008 RIN:0579-AC68


Comment from Terry Singeltary Document ID: APHIS-2008-0010-0008 Document Type: Public Submission This is comment on Proposed Rule: Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products Docket ID: APHIS-2008-0010 RIN:0579-AC68


Topics: No Topics associated with this document View Document: More


Document Subtype: Public Comment Status: Posted Received Date: March 22 2012, at 12:00 AM Eastern Daylight Time Date Posted: March 22 2012, at 12:00 AM Eastern Daylight Time Comment Start Date: March 16 2012, at 12:00 AM Eastern Daylight Time Comment Due Date: May 15 2012, at 11:59 PM Eastern Daylight Time Tracking Number: 80fdd617 First Name: Terry Middle Name: S. Last Name: Singeltary City: Bacliff Country: United States State or Province: TX Organization Name: CJD TSE PRION Submitter's Representative: CONSUMERS


Comment: comment submission Document ID APHIS-2008-0010-0001 Greetings USDA, OIE et al, what a difference it makes with science, from one day to the next. i.e. that mad cow gold card the USA once held. up until that fateful day in December of 2003, the science of BSE was NO IMPORTS TO USA FROM BSE COUNTRY. what a difference a day makes$ now that the shoe is on the other foot, the USDA via the OIE, wants to change science again, just for trade $ I implore the OIE decision and policy makers, for the sake of the world, to refuse any status quo of the USA BSE risk assessment. if at al, the USA BSE GBR should be raise to BSE GBR IV, for the following reasons. North America is awash with many different TSE Prion strains, in many different species, and they are mutating and spreading. IF the OIE, and whatever policy makers, do anything but raise the risk factor for BSE in North America, they I would regard that to be highly suspicious. IN fact, it would be criminal in my opinion, because the OIE knows this, and to knowingly expose the rest of the world to this dangerous pathogen, would be ‘knowingly’ and ‘willfully’, just for the almighty dollar, once again. I warned the OIE about all this, including the risk factors for CWD, and the fact that the zoonosis potential was great, way back in 2002. THE OIE in collaboration with the USDA, made the legal trading of the atypical Nor-98 Scrapie a legal global commodity. yes, thanks to the OIE and the USDA et al, it’s now legal to trade the atypical Nor-98 Scrapie strain all around the globe. IF you let them, they will do the same thing with atypical BSE and CWD (both strains to date). This with science showing that indeed these TSE prion strains are transmissible. I strenuously urge the OIE et al to refuse any weakening to the USA trade protocols for the BSE TSE prion disease (all strains), and urge them to reclassify the USA with BSE GBR IV risk factor. SEE REFERENCE SOURCES IN ATTACHMENTS


SEE Terry S. Singeltary Sr. Attachment WORD FILE ;














Sunday, March 11, 2012


APHIS Proposes New Bovine Spongiform Encephalopathy Import Regulations in Line with International Animal Health Standards Proposal Aims to Ensure Health of the U.S. Beef Herd, Assist in Negotiations






MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...


***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model




***Infectivity in skeletal muscle of BASE-infected cattle




***feedstuffs- It also suggests a similar cause or source for atypical BSE in these countries.




***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans.




Sunday, May 6, 2012


Bovine Spongiform Encephalopathy Mad Cow Disease, BSE May 2, 2012 IOWA State University OIE






Friday, May 11, 2012


Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits







TSS

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