From: TSS(216-119-162-38.ipset44.wt.net) Subject: Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States [FULL TEXT] Date: February 22, 2003 at 7:38 am PST
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Ermias D. Belay, MD; Ryan A. Maddox, MPH; Pierluigi Gambetti, MD; and Lawrence B. Schonberger, MD
Abstract—Transmissible spongiform encephalopathies (TSEs) attracted increased attention in the mid-1980s because of the emergence among UK cattle of bovine spongiform encephalopathy (BSE), which has been shown to be transmitted to humans, causing a variant form of Creutzfeldt-Jakob disease (vCJD). The BSE outbreak has been reported in 19 European countries, Israel, and Japan, and human cases have so far been identified in four European countries, and more recently in a Canadian resident and a US resident who each lived in Britain during the BSE outbreak. To monitor the occurrence of emerging forms of CJD, such as vCJD, in the United States, the Centers for Disease Control and Prevention has been conducting surveillance for human TSEs through several mechanisms, including the establishment of the National Prion Disease Pathology Surveillance Center. Physicians are encouraged to maintain a high index of suspicion for vCJD and use the free services of the pathology center to assess the neuropathology of clinically diagnosed and suspected cases of CJD or other TSEs.
NEUROLOGY 2003;60:176–181
Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are neurodegenerative disorders that occur in humans and animals. They are believed to be caused by the accumulation in neurons of an abnormal isoform of a membrane glycoprotein known as the prion protein. TSEs in humans generally occur as a rare, sporadic disease with no recognizable pattern of transmission or as a familial disease associated with prion protein gene mutations.1 Iatrogenic transmission of Creutzfeldt-Jakob disease (CJD) is relatively uncommon, but may occur in outbreaks (e.g., human growth hormone–associated CJD) that can be controlled with the implementation of appropriate preventive measures.2-4 In the 1980s, the emergence in Europe of a large outbreak of bovine spongiform encephalopathy (BSE) in cattle and, more recently, an outbreak of a new variant form of CJD (vCJD) in humans linked with food-borne transmission of the BSE agent has raised serious concerns about the geographic spread and ultimate number of cases of these diseases. In April 2002, a probable case of vCJD was identified in a Florida resident who was born in Britain and raised there throughout the 1980s, a period when the BSE outbreak was rising and no control measures to prevent human exposure were instituted. Increased concern about the occurrence of TSEs led to increased surveillance and implementation of BSE control measures in the United States and other countries currently free of endemic BSE and vCJD.
The presumed food-borne transmission of BSE to humans has also raised concerns about the possible zoonotic transmission of chronic wasting disease (CWD) of deer and elk.5 CWD was first recognized in the late 1960s among captive mule deer housed in research facilities in Fort Collins, CO. Since then, the disease has been shown to be endemic among free-ranging deer and elk in northeastern Colorado and southeastern Wyoming.6 From 2000 through 2002, CWD in free-ranging deer was detected in locations outside of the known endemic areas in western Colorado, Nebraska, New Mexico, South Dakota, Wisconsin, and Saskatchewan, Canada. Beginning in 1996, outbreaks of CWD in privately-owned elk farms were reported in different parts of the United States and Canada, including Alberta, Colorado, Kansas, Montana, Nebraska, Oklahoma, Saskatchewan, and South Dakota.7
Bovine spongiform encephalopathy. BSE was first identified as an emerging TSE in 1986 in the United Kingdom where it caused a major outbreak among cattle that is now on the decline. Statistical models have indicated that the first BSE cases may have occurred in the early 1980s.8 As of June 30, 2002, over 179,300 cases of BSE had been confirmed in Great Britain; 1,032 of the cases occurred in 2001 and 665 during the first half of 2002.9 However, the actual number of cattle infected with the BSE agent has been estimated to be around 1 million.10 BSE is believed to have resulted from the feeding of cattle with contaminated protein-rich meat-and-bone meal produced by rendering discarded animal carcasses.11 The leading hypotheses for the origin of BSE include contamination of the meat-and-bone meal by an agent causing scrapie in sheep or by a spontaneously occurring, unrecognized BSE in cattle. Before the late 1970s, rendering of carcasses to produce meatand- bone meal had included a solvent extraction and solvent recovery steps that subjected the rendered material to prolonged heating in the presence of a hydrocarbon solvent. Omission of these treatment steps in the late 1970s and early 1980s in most rendering plants in the United Kingdom is believed to have contributed to the emergence of BSE by allowing passage of the infective agent to the finished product.11 As more cattle died of BSE, their carcasses continued to be rendered and fed to other cattle, and this practice amplified the BSE outbreak until the use of ruminant protein in ruminant feed was banned in the United Kingdom in 1988.11,12 Consistent with the 2- to 8-year incubation period of the disease in cattle, the BSE outbreak in the United Kingdom declined beginning in 1993, about 5 years after the feed ban, although cases continue to occur at a much lower rate. The continued occurrence of BSE, particularly among cattle born after the 1988 ban, was primarily attributed to cross-contamination of cattle feed by feed intended for nonruminant species that could have been contaminated by BSE.13
In 1989, the concern that BSE may cross species and infect humans precipitated a ban in the United Kingdom to exclude specified risk materials (e.g., brain, spinal cord, distal ileum) from cattle products destined for human consumption.12 The UK preventive measures were increasingly tightened, and a policy was put in place in 1996 to prevent cattle aged 30 months, regardless of their health status, from entering the human or animal food chains.13
Elsewhere in Europe, through 1999, the occurrence of BSE among native cattle had been reported in Belgium, France, Ireland, Liechtenstein, Luxembourg, Netherlands, Portugal, and Switzerland.14
From 2000 through 2001, the reported incidence of BSE rose in some of these European countries, and initial indigenous BSE cases were detected in Austria, the Czech Republic, Denmark, Finland, Germany, Greece, Italy, Japan, Slovakia, Slovenia, and Spain. The growing number of countries with endemic BSE led to increased public concern about the safety of European and Japanese cattle products. In response to these BSE outbreaks, the European Commission proposed a temporary prohibition of the use of animal protein in all farmed animals, pending re-evaluation of other control measures adopted by the member states.15 These control measures, which varied by country, included ruminant feed bans, removal of specified risk materials, such as the brain and spinal cord, from cattle products intended for human use, and mandatory brain testing of cattle older than 30 months that are destined for human consumption. Most recently, during the first half of 2002, Israel and Poland reported their first indigenous BSE cases. BSE in imported cattle only, in the absence of indigenous cases, was reported in Canada (1 case), Falkland Islands (1 case), and Oman (2 cases).14
Since 1989, to prevent the introduction of BSE into the United States, the US Department of Agriculture (USDA) restricted the importation of live cattle and certain cattle products from the United Kingdom and other BSE-endemic countries. In 1997, this restriction was expanded to prohibit importation of cattle and certain cattle products from all European countries, and most recently from Japan and Israel. In addition, the USDA trained veterinarians and veterinary laboratory workers on the clinical and pathologic manifestations of BSE and instituted an ongoing BSE surveillance program.16 As of September 2002, these USDA surveillance efforts, including analysis of brain specimens from 36,594 cattle, had detected no evidence of the occurrence of BSE in the United States. To provide protection against the spread of BSE should it be introduced into the United States, the Food and Drug Administration (FDA) published a final rule in 1997 that prohibited the use of most mammalian protein, particularly ruminant tissues, in the manufacture of ruminant feed.17,18
Variant Creutzfeldt-Jakob disease. Variant CJD was reported as a distinct disease entity in April 1996 after the UK government’s expert advisory committee announced its conclusion that the BSE agent may have crossed the species barrier, causing an outbreak of the disease in humans.19 The possibility that BSE could cross the species barrier to infect humans had been suspected about 6 years earlier with the identification among domestic cats in the United Kingdom of feline spongiform encephalopathy, whose agent characteristics were similar to the BSE agent. Transmission of the BSE agent presumably via ingestion of contaminated feed has also been reported in exotic ungulates and wild cats in British zoos.11
As of October 4, 2002, a total of 138 vCJD cases had been reported: 128 definite or probable cases in the United Kingdom (includes one UK resident who was hospitalized and died in Hong Kong), 6 in France, and 1 each in Canada, Ireland, Italy, and the United States.12,20-22 The Canadian, Irish and US cases resided in the United Kingdom during a key exposure period of the UK population to the BSE agent. The continued occurrence of vCJD cases only in persons who have lived in BSE-endemic areas, particularly the United Kingdom where most BSE cases were identified, and several animal and molecular laboratory studies provide strong evidence that vCJD is causally linked with BSE.23-27
January (2 of 2) 2003 NEUROLOGY 60 177
Statistical analysis of the numbers of definite and probable vCJD cases reported through June 2000 indicated an increasing trend for the vCJD outbreak in the United Kingdom.28 However, the persistency of this increasing trend or the eventual magnitude of the vCJD outbreak remains unknown. From statistical models, UK researchers had predicted that the total number of vCJD cases would likely range between 70 and 136,000, depending upon various assumptions about the mean incubation period.29 Two recently published studies using other statistical models suggested that the UK vCJD outbreak might not exceed several hundred clinical cases.30,31 One of these studies pointed out the possibility that the incubation period could be so long that even if millions of persons were infected with the agent of vCJD, a large majority of these people could die of other competing causes before they developed the TSE illness. 31 Such infected persons could pose a potential, albeit unknown, risk for secondary transmission of the agent (e.g., transmissions by contaminated surgical instruments).
A most striking feature of patients with vCJD compared with patients who have classic CJD is their unusually young age at the time of illness onset. 18,32 On the basis of the initially reported 110 vCJD deaths in the United Kingdom, the median age at death was 28 years; 60% died at 30 years of age, and approximately 13% died as teenagers (R.G. Will, personal communication, 2002). In addition to the age distribution, the clinicopathologic profile of patients with vCJD and immunoblot characteristics of the vCJD agent differed from that seen in patients with classic CJD (table 1). The UK patients with vCJD usually presented with early and persistent psychiatric symptoms, commonly with depression, anxiety, and withdrawal.32 Some of the patients were initially regarded as having a primary psychiatric illness and were treated by a psychiatrist early in the course of the disease. Evaluation of the clinical manifestations of the first 100 patients with vCJD in the United Kingdom indicated that the onset of frank neurologic signs such as gait disturbance, slurring of speech, and tremor was usually delayed by several months after illness onset.32,33 The most striking early neurologic sign in some of these patients was persistent dysesthesia or paresthesia. Other neurologic signs, including chorea, dystonia, and myoclonus, frequently developed late during the course of the illness (see the Appendix). None of the vCJD cases reported to date had the EEG tracing of periodic triphasic complexes often seen in patients with sporadic CJD. In addition, a prominent, symmetric pulvinar high signal on T2-weighted or proton density–weighted MRI has been reported in about 78% of patients with vCJD.34 This prominent pulvinar high signal has been designated the “pulvinar sign.” The MRI high signals have been shown to correlate with underlying neuropathologic findings of astrocytosis and neuronal loss. The polymorphic codon 129 of the prion protein gene in all patients with vCJD on whom genetic studies have been performed was shown to be homozygous for methionine.31
Neuropathologic evaluation of a brain autopsy specimen is required for a confirmatory diagnosis of vCJD. In addition to the presence of the typical spongiosis, gliosis, and neuronal loss that are considered a hallmark of CJD, the neuropathologic characteristics of vCJD include the presence of numerous amyloid plaques that are surrounded by a halo of spongiform changes, resembling the “florid plaques” first described in experimental transmission of Icelandic scrapie in mice.35 In addition, immunohistochemical staining demonstrates marked accumulation of the diseaseassociated prion protein in diffuse or pericellular deposits in the cerebrum and cerebellum. Detection of the protease-resistant prion protein by immunohistochemical and immunoblot analyses outside of the brain in lymph nodes, spleen, and tonsils of patients with vCJD has been reported.36,37 On immunoblot analysis, the protease-resistant prion protein fragment from patients with vCJD characteristically has a glycoform ratio that has not been described in sporadic CJD.38
Table Clinical and laboratory characteristics distinguishing variant Creutzfeldt-Jakob disease (CJD) from the classic form of CJD
Characteristics Variant CJD Classic CJD
Median age at death, y 28 68
Clinical presentation Psychiatric or sensory symptoms; delayed appearance of neurologic signs Dementia associated with neurologic signs
Median illness duration, mo 13 4
Periodic short waves on EEG tracings Absent In about 75% of patients Symmetrical pulvinar high signal on MRI In over 75% of patients Not reported
Numerous “florid plaques” on neuropathology In all patients Absent
Immunohistochemical analysis of brain tissue Marked accumulation of PrPres Variable
Increased glycoform ratio on immunoblot analysis of PrPres In all patients Not reported
Presence of infective agent in lymphoid tissues Readily detected Not readily detected
PrPres Protease-resistant prion protein.
178 NEUROLOGY 60 January (2 of 2) 2003
The reason for the predominant occurrence of vCJD among patients under 30 years of age is unknown. Differential consumption of potentially contaminated meat products by the younger population has been suggested as a possible contributory factor to the age distribution of vCJD.39 However, vCJD has been confirmed in a 74-year-old man who died in 1999, 7 months after illness onset.40 The older patient’s clinical and pathologic phenotype and methionine homozygosity at codon 129 were similar to that of other patients with vCJD. He presented with psychiatric symptoms and was initially admitted to a psychiatric unit and treated for a psychotic illness. The patient became increasingly forgetful and unsteady and had recurrent falls. He had complaints of various episodes of pain for which no cause could be established. Histopathologic examination of the brain autopsy tissue showed the presence of florid plaques in large numbers in the cerebral and cerebellar cortices. Although clearly an outlier, the identification of vCJD in a patient at 74 years of age indicates that some persons in older age groups can potentially be susceptible to contracting vCJD.
Creutzfeldt-Jakob disease surveillance in the United States.
The emergence of BSE and vCJD in Europe created a concern that US residents might be exposed to BSE-contaminated cattle products from Europe or to possibly unrecognized BSE in the United States. For example, concern was raised about the possibility that US residents who traveled or resided in the United Kingdom or other BSE-endemic countries since 1980 could potentially have been exposed to the BSE agent. In April 2002, the first case of vCJD in a US resident was reported in a 22-year-old Florida patient who was born and raised in Britain and moved to the United States in 1992. As of October 2002, the patient, whose illness began in November 2001, was still alive. Her illness fulfills UK criteria for probable vCJD.
In 1998, the American Medical Association Council on Scientific Affairs called for increased CJD surveillance to monitor the possible occurrence of vCJD in the United States.41 Among other recommendations, the council indicated that physicians should become knowledgeable about BSE to be able to advise their patients about the possible risk of exposure to the BSE agent during travel abroad. To facilitate such advice to travelers, CDC provides a traveler’s advisory about the possible risk of BSE exposure during travel to Europe.42 There is also a concern about a possible, albeit theoretical, risk of secondary person-to-person transmission of the vCJD agent via blood and blood products. This risk is considered theoretical because no convincing evidence for transmission of either classic CJD or vCJD via blood or blood products has been reported in the human population. However, the world’s limited experience with vCJD, the presence of the vCJD agent in lymphoid tissues of infected patients, and transmission of the BSE agent by blood transfusion in an experimental sheep model during the incubation period contributed to the concern about the possible transmission of the vCJD agent through the blood supply.43 This concern is further complicated by the long incubation period of the disease. Because the incubation period is measured in years or decades, should blood-borne transmissions occur in humans, many recipients would have been exposed before the first blood-borne infection is detected. Additional concerns have also been raised about the potential for person-to-person spread of the vCJD agent by surgical instruments coming in contact with infected tissues, such as lymphoid tissues of patients incubating vCJD.
Because the most likely source of exposure to the BSE agent for US residents is consumption of contaminated food in the United Kingdom, the FDA in 1999 instituted a deferral policy to exclude from donating blood any person who traveled to the United Kingdom for a cumulative period of 6 months or more between 1980 and 1996. The Transmissible Spongiform Encephalopathy Advisory Committee of the FDA recently recommended further tightening the UK travel criteria to a cumulative period of 3 months or more and added additional deferral criteria, including the exclusion of donors who visited or resided in other European countries for a cumulative period of 5 years or more during 1980 to the present.44
In 1996, after vCJD was reported in the United Kingdom, the CDC enhanced its CJD surveillance to monitor the possible occurrence of the disease in the United States. One enhancement, which focused on the striking difference in age distribution of vCJD, included periodic review of national CJD mortality data to monitor any increase in the occurrence of CJD among unusually young patients. In collaboration with state and local health authorities, the CDC initiated follow-up investigations of patients with CJD younger than 55 years through reviews of their clinical and neuropathologic records. In addition, in collaboration with the American Association of Neuropathologists, the CDC established the National Prion Disease Pathology Surveillance Center at Case Western Reserve University, Cleveland, OH.45,46 Through its contacts with US pathologists, this center helps to monitor for the occurrence of vCJD and other potentially emerging human TSEs in the United States regardless of the age of the patient or clinical diagnosis. It also makes available state-ofthe- art free diagnostic services for physiciandiagnosed or suspected cases of TSE in humans. Physicians are encouraged to make all efforts to arrange for a brain autopsy in all such cases and to take advantage of the free diagnostic services provided by the National Prion Disease Pathology Surveillance Center to assess the neuropathology of the patients. Given the many unknowns associated with TSEs, such assessments would not only help to confirm clinical diagnoses of these diseases, but also help to monitor the occurrence of a new TSE, such as vCJD or possibly a human form of CWD, in the United States. More detailed information about the activities of the Center can be obtained at its website.47
January (2 of 2) 2003 NEUROLOGY 60 179
Is chronic wasting disease transmissible to humans or cattle?
The occurrence of CWD in several states that were not known to be endemic foci for the disease has increased the concern about a widespread outbreak of CWD in many areas of the country, and its possible transmission to humans and domestic animals such as cattle. A recently published experimental study has demonstrated transmission of the CWD agent to cattle by intracerebral inoculation.48 An experiment to determine susceptibility of cattle to CWD by oral challenge is currently in progress. The efficiency by which CWD-associated prions influence the conversion of prion protein from different sources, including cervids, cattle, and humans, has been evaluated by cell-free conversion experiments. 49,50 The cell-free prion protein conversion reactions are believed to assess the molecular compatibility of disease-associated prions from one species with normal prion protein obtained from different species. These cell-free conversion experiments indicated that the efficiency of CWDassociated prions in converting bovine prion protein was an average of at least 5- to 12-fold weaker than the homologous conversion of cervid prion protein and bovine prion protein. Similar experiments indicated that the efficiency of CWD-associated prions in converting human prion protein was over 14-fold weaker than the homologous conversion of cervid prion protein and over fivefold weaker than the homologous conversion induced by CJD-associated prions. Although conversion studies showed some degree of incompatibility of cervid prion protein with that of cattle and humans, the authors indicated that it may be premature to draw firm conclusions about CWD naturally transmitting to humans or cattle. Lack of efficient cellfree conversion of human prion protein by BSEassociated prions has also been reported, despite the fact that BSE has been shown to be transmitted to humans.49 The authors of the cell-free conversion studies also indicated that other factors are important in determining in vivo transmission of TSE agents between species, including dose and strain of the agent, route of infection, stability of the agent inside and outside of the host, and the efficiency of agent delivery to the nervous system.
A recent epidemiologic and laboratory investigation of three unusually young patients with CJD who regularly consumed venison did not identify convincing evidence for a causal link between CWD and the patients’ illness.5 Two of the patients, aged 28 and 30 years at death, were hunters, and the third patient, aged 28 years, consumed venison harvested by family members. None of the patients was reported to have consumed deer meat obtained from the known CWDendemic areas of Colorado and Wyoming. The patients’ disease phenotype and the prion protein gene polymorphism at codon 129 were heterogeneous, possibly indicating lack of exposure to a similar agent. This was unlike patients with vCJD in whom the disease phenotype and codon 129 polymorphism had some homogeneity, owing to infection of the patients by the same agent of BSE. In addition, brain tissues from over 1,000 deer and elk harvested in the areas where the venison consumed by the three patients originated from tested negative for CWD.
Although strong evidence for CWD transmission to humans is lacking, it should be recognized that limited studies designed to seek such evidence have been conducted. Given the BSE experience in Europe where an animal TSE previously believed to be nonpathogenic to humans was later shown to be responsible for an outbreak of vCJD, both epidemiologic and laboratory studies and ongoing CJD surveillance remain critical for continuing to assess the risk, if any, of CWD transmission to humans.
Appendix
The following are prominent clinical features that lead to a suspected diagnosis of variant Creutzfeldt-Jakob disease (CJD):
1. Young age of the patient (commonly 55 years). 2. Early psychiatric symptoms or persistent painful sensory symptoms such as dysesthesia or paresthesia. 3. Dementia and delayed appearance of ataxia and at least one of the following three neurologic signs: myoclonus, chorea, or dystonia. 4. A normal or abnormal EEG but not the diagnostic EEG changes often seen in classic CJD. 5. A prominent, symmetrical pulvinar high signal on T2-weighted or proton density–weighted MRI. 6. Duration of illness of at least 6 months. 7. Routine investigations of the patient do not suggest an alternative non-CJD diagnosis. 8. No history of receipt of cadaveric human pituitary growth hormone or a dura mater graft. 9. No history of CJD in a first-degree relative or absence of prion protein gene mutation in the patient. Acknowledgment The authors thank John O’Connor for his suggestions and editorial assistance. References 1. Belay ED. Transmissible spongiform encephalopathies in humans. Annu Rev Microbiol 1999;53:283–314. 2. Brown P, Preece M, Brandel JP, et al. Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 2000;55:1075–1081. 3. Fradkin JE, Schonberger LB, Mills JL, et al. Creutzfeldt-Jakob disease in pituitary growth hormone recipients in the United States. JAMA 1991;265:880–884. 4. Centers for Disease Control and Prevention. Creutzfeldt-Jakob disease associated with cadaveric dura mater grafts—Japan, January 1979– May 1996. MMWR Morb Mortal Wkly Rep 1997;46:1066–1069. 5. Belay ED, Gambetti P, Schonberger LB, et al. Creutzfeldt-Jakob disease in unusually young patients who consumed venison. Arch Neurol 2001;58:1673–1678. 6. Laplanche JL, Hunter N, Shinagawa M, Williams E. Scrapie, chronic wasting disease, and transmissible mink encephalopathy. In: Prusiner SB, ed. Prion biology and diseases. Cold Spring, NY: Cold Spring Laboratory Press, 1999;393–429. 7. Southeastern Cooperative Wildlife Disease Study, College of Veterinary Medicine, The University of Georgia. Special CWD issue. SCWDS Briefs 2002;18:1–17. 8. Cohen CH, Valleron AJ. When did bovine spongiform encephalopathy (BSE) start? Implications on the prediction of a new variant of Creutzfeldt-Jakob disease (vCJD) epidemic. Int J Epidemiol 1999;28: 526–531. 9. Department of Environment, Food and Rural Affairs, United Kingdom. BSE. Available at: http://www.defra.gov.uk/animalh/bse/index.html. Accessed October 29, 2002. 180 NEUROLOGY 60 January (2 of 2) 2003 10. Anderson RM, Donnelly CA, Ferguson NM, et al. Transmission dynamics and epidemiology of BSE in British cattle. Nature 1996;382:779– 788. 11. Collee JG, Bradley R. BSE: a decade on—part 1. Lancet 1997;349:636– 641. 12. Brown P, Will RG, Bradley R, Asher DM, Detwiler L. Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: background, evolution, and current concerns. Emerg Infect Dis 2001;7:6–16. 13. Collee JG, Bradley R. BSE: a decade on—part 2. Lancet 1997;349:715– 721. 14. Office International Des Epizooties. Number of reported cases of bovine spongiform encephalopathy (BSE) worldwide. Available at: http:// www.oie.int/eng/info/en_esbmonde.htm. Accessed April 1, 2002. 15. European Commission. Available at: http://www.europa.eu.int/eur-lex/ en/com/paf/2000/en_500PC0820.html. Accessed October 29, 2002. 16. U.S. Department of Agriculture, Animal and Plant Health Inspection Service. BSE surveillance. Available at: http://www.aphis.usda.gov/oa/ bse/bsesurvey.pafl#charts. Accessed July 19, 2002. 17. Nightingale SL. Ruminant-to-ruminant feeding ban proposed to reduce risk of transmissible spongiform encephalopathies. JAMA 1997;277:370. 18. Schonberger LB. New variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Infect Dis Clin North Am 1998;12:111–121. 19. Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt- Jakob disease in the UK. Lancet 1996;347:921–925. 20. Department of Health, United Kingdom. Monthly Creutzfeldt-Jakob disease statistics. Available at: http://www.doh.gov.uk/cjd/stats/ oct02.htm. Accessed October 29, 2002. 21. Institut de Veille Sanitaire. Nombre de cas de maladie de Creutzfeldt- Jakob. Available at: http://www.invs.sante.fr/display/?docpublications/ mcj/donnees_mcj.html. Accessed April 8, 2002. 22. Kay R, Lau WY, Ng HK, Chan YL, Lyon DJ, van Hasselt CA. Variant Creutzfeldt-Jakob disease in Hong Kong. Hong Kong Med J 2001;7: 296–298. 23. Bruce ME, Will RG, Ironside JW. Transmission to mice indicates that ‘new variant’ CJD is caused by the BSE agent. Nature 1997;389:498–501. 24. Collinge J, Sidle KCL, Heads J, Ironside J, Hill AF. Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 1996;383:685–690. 25. Lasmézas CI, Deslys JP, Demaimay R, et al. BSE transmission to macaques. Nature 1996;381:743–744. 26. Scott MR, Will R, Ironside J, et al. Compelling transgenic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc Natl Acad Sci USA 1999;96:15137–15142. 27. Belay ED, Potter ME, Schonberger LB. Relationship between transmissible spongiform encephalopathies in animals and humans. In: Task Force Report of the Council for Agricultural Science and Technology. No. 136. Washington, DC: Council for Agricultural Science and Technology, 2000;20–21. 28. Andrew NJ, Farrington CP, Cousens SN, et al. Incidence of variant Creutzfeldt-Jakob disease in the UK. Lancet 2000;356:481–482. 29. Ghani AC, Ferguson NM, Donnelly CA, Anderson RM. Predicted vCJD mortality in Great Britain. Nature 2000;406:583–584. 30. Valleron AJ, Boelle PY, Will R, Cesbron JY. Estimation of epidemic size and incubation time based on age characteristics of vCJD in the United Kingdom. Science 2001;294:1726–1728. 31. Huillard d’Aignaux JN, Cousens SN, Smith PG. Predictability of the UK variant Creutzfeldt-Jakob disease epidemic. Science 2001;294: 1729–1731. 32. Will RG, Zeidler M, Stewart GE, et al. Diagnosis of new variant Creutzfeldt-Jakob disease. Ann Neurol 2000;47:575–582. 33. Spencer MD, Knight RSG, Will RG. First hundred cases of variant Creutzfeldt-Jakob disease: retrospective case note review of early psychiatric and neurological features. BMJ 2002;324:1479–1482. 34. Zeidler M, Sellar RJ, Collie DA, et al. The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease. Lancet 2000; 355:1412–1418. 35. Ironside JW. Neuropathological findings in new variant CJD and experimental transmission of BSE. FEMS Immunol Med Microbiol 1998;21: 91–95. 36. Hill AF, Zeidler M, Ironside J, Collinge J. Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy. Lancet 1997;349:99–100. 37. Hill AF, Butterworth RJ, Joiner S, et al. Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999;353:183–189. 38. Parchi P, Capellari S, Chen SG, et al. Typing prion isoforms. Nature 1997;386:232–233. 39. Gore SM, Bingham S, Day NE. Age related dietary exposure to meat products from British dietary surveys of teenagers and adults in the 1980s and 1990s. BMJ 1997;315:404–405. 40. Lorains JW, Henry C, Agbamu DA, et al. Variant Creutzfeldt-Jakob disease in an elderly patient. Lancet 2001;357:1339–1340. 41. Tan L, Williams MA, Khan MK, Champion HC, Nielsen NH. Risk of transmission of bovine spongiform encephalopathy to humans in the United States: report of the council on scientific affairs. JAMA 1999; 281:2330–2339. 42. Centers for Disease Control and Prevention. Update 2002: bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease. Available at: http://www.cdc.gov/ncidod/diseases/cjd/cjd.htm. Accessed October 29, 2002. 43. Houston F, Foster JD, Chong A, Hunter N, Bostock CJ. Transmission of BSE by blood transfusion in sheep. Lancet 2000;356:999–1000. 44. Food and Drug Administration. Guidance for industry: revised preventive measures to reduce the possible risk of transmission of Creutzfeldt- Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD) by blood and blood products. Available at: http://www.fda.gov/cber/gdlns/ cjdvcjd.pdf. Accessed April 1, 2002. 45. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt- Jakob disease in the United States: 1979–1998. JAMA 2000;284:2322– 2323. 46. Holman RC, Khan AS, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States, 1979–1994: using national mortality data to assess the possible occurrence of variant cases. Emerg Infect Dis 1996;2:333–337. 47. National Prion Disease Pathology Surveillance Center (homepage). Available at: http://www.cjdsurveillance.com. Accessed April 1, 2002. 48. Hamir AN, Cutlip RC, Miller JM, et al. Preliminary findings on the experimental transmission of chronic wasting disease agent of mule deer to cattle. J Vet Diagn Invest 2001;13:91–96. 49. Raymond GJ, Hope J, Kocisko DA, et al. Molecular assessment of the potential transmissibilities of BSE and scrapie to humans. Nature 1997;388:285–288. 50. Raymond GJ, Bossers A, Raymond LD, et al. Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. EMBO 2000;19:4425–4430. January (2 of 2) 2003 NEUROLOGY 60 181
i would like to respond to the above article. i will first post my submission to the Neurology Journal about this article with replies (i do not know if they will publish any of it me being the ''lay person'' et al). probably will rule out any of it getting published after me posting this to WWW, but i could not hold this data with the recent news media reports and insinuations of no CWD transmission to man. there are just too many hunters and family and friends of hunters, with freezer's full of venison, that will take these 'false assurances' to heart. so i would like to post some facts (fact is, they still don't know). then i will post some transmission studies, then some private comments from other well known and respected TSE Scientist, some data i have accumulated (some never posted), and some questions...
Subject: RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States Date: Mon, 27 Jan 2003 17:29:36 -0600 From: "Terry S. Singeltary Sr." To: "Terry S. Singeltary Sr."
Thank you for your Post-Publication Peer Review
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RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Terry S. Singeltary, retired (medically) CJD WATCH
Send Post-Publication Peer Review to journal: Re: RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States
Email Terry S. Singeltary: flounder@wt.net
Greetings,
i lost my Mother to hvCJD (Heidenhain Variant CJD) 12/14/97, so i would like to make several comments on the attempt to monitor the occurrence of emerging forms of CJD that the CDC and the National Prion Disease Pathology Surveillance Center are attempting;
1st, i find it very disturbing, that with the findings from Asante, Collinge et al that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc, the commonest sporadic CJD, i find it very disturbing that the CDC and NPDP still refuse to make CJD and all human TSEs reportable nationally. CJD and all human TSEs _must_ be made reportable in every State and Internationally ASAP.
2nd, i also find it very disturbing that the only CJD Questionnaire that the CDC and Case Western is using (when they decide to issue one), i find it very disturbing that this CJD Questionnaire asks absolutely not one question as to route and source. Only how the disease was diagnosed. how will the route and source of this agent ever be traced in the USA if we do not ask the questions pertaining to route and source? i only hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJDs which is sporadic CJD, is all spontaneous, without route/source.
we have many TSEs in the USA in both animal and man, and they are spreading. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, sheep, cattle, and to the primate by inoculation, humans are primates, so i would take these findings very seriously. with the known incubation periods in other TSEs, oral transmission studies of this may take much longer. also, another cow has gone down with CWD by inoculations, this brings to 4 cattle infected with CWD by inoculation. also, considering the fact the late Richard Marsh already has shown some TSE to exist in the USA bovine, all this should warrant immediate actions pertaining to making CJD/human TSEs reportable in every state. we must issue a CJD Questionnaire to every victim/family of CJD/TSEs to be filled out and to ask _real_ questions as pertaining to route and source of this agent. to prolong this, will only spread the agent and further expose many humans needlessly. also with Asante and Collinge et al findings, 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?
-------- Original Message -------- Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD Date: Thu, 28 Nov 2002 10:23:43 -0000 From: "Asante, Emmanuel A" To: "'flounder@wt.net'"
Dear Terry,
I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention. Thank you for your interest in the paper.
In respect of your first question, the simple answer is, yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD.
It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc.
I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes.
Emmanuel Asante
<> ____________________________________
Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until 9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now) ____________________________________
Diagnosis and Reporting of Creutzfeldt-Jakob Disease T. S. Singeltary, Sr; D. E. Kraemer; R. V. Gibbons, R. C. Holman, E. D. Belay, L. B. Schonberger
#Docket No. 01-068-1 Risk Reduction Strategies for Potential BSE Pathways Involving Downer Cattle and Dead Stock of Cattle and Other Species - TSS 1/21/03 (2)
In Reply to: Docket No. 01-068-1 Risk Reduction Strategies for Potential BSE Pathways Involving Downer Cattle and Dead Stock of Cattle and Other Species [TSS SUBMISSION] January 21, 2003
Subject: Letter to Neurology Date: Mon, 3 Feb 2003 12:03:03 -0500 From: XXXXXXXXXXXXXXXXXXXX To: "'flounder@wt.net'"
Dear Terry Singletary: We do not, as a rule, post letters from the lay public. However, we are having your letter reviewed. We will let you know the disposition within one week. Sincerely, XXXXXX Editor-in-Chief Neurology
~~~~~~~~~~~ XXXXXXX Managing Editor Neurology online [www.neurology.org] 1351 Mount Hope Ave. Suite 203 Rochester, NY 14620 tel. (585) 275-5858 fax (585) 271-2009
=========================================
Subject: Re: Letter to Neurology Date: Mon, 03 Feb 2003 12:33:04 -0600 From: "Terry S. Singeltary Sr." To: XXXXXXXXX References: <4FF126AF9EE8D4118D720003470BE9E105720437@exmc4.urmc.rochester.edu>
Greetings Neurology and hello Dr. Griggs and Kathy,
> We do not, as a rule, post letters from the lay public.
i know some that would dispute this about me being a ''lay public'' ;-)
a private email from the late Dr. Gibbs, a true pioneer in the research of human/animal TSEs and one that never wavered on helping the families and victims of this horrible disease, and one that helped me many times in trying to seek out the truth;
Subject: Re: Hello Dr. Gibbs........... Date: Wed, 29 Nov 2000 14:14:18 -0500 From: "Clarence J. Gibbs, Jr., Ph.D." To: "Terry S. Singeltary Sr." References: <3A254430.9FB97284@wt.net>
Hi Terry: 326 E Stret N.E., Washington, D. C. 20002. Better shrimp and oysters than cards!!!! Have a happy holiday and thanks for all the information you bring to the screen. Joe Gibbs ==========
although i still cannot dispute the fact i have no PhDs:-(
but this should/does not alter the facts in my research.
however i am very grateful you are even considering a publishing of my rebuttal to the article, honored in fact. and i thank you for that. those 2 items i proposed are very important to the finding of route and source of TSE agent, and the finding of the true extent of these TSEs and to the protection of public health in the USA and i would hope Globally.
i should quit while i am ahead at this point, but i find it very important, that since you are even considering my short reply, you should at least have this other very important data, if for nothing else, your own personal use.
i have pasted the CJD surveillance unit in the USA (New CJD Foundation CJD Questionnaire at Case Western) CJD Questionnaire and the CJD Questionnaire i proposed, and also some critical data on _endoscopy_ equipment and CJD/TSEs for you to evaluate/compare and/or for your private use, and the Warning from the W.H.O. this week about Global BSE/TSEs and the 'audio' interview with Dr. Ricketts below, speaking about a new study about .1 gram of BSE as being lethal;
CJD FOUNDATION QUESTIONNAIRE CASE WESTERN
REPORT FOR DATA BASE OF PATIENTS WITH CREUTZFELDT--JAKOB DISEASE (CJD) OR OTHER TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES (TSE's)
Name of Patient*: (not required; if provided, must be with express consent of family member)
Date form filled out: / / (mm/dd/yy)
Person filling out form:
Relationship of person filling out form to patient:
Location where patient died: State: County: City:
Location where patient resided: State: County: City:
Sex of patient: male female unknown
Race of patient: white African-American -- Asian/Pacific Islander American-Indian/Alaskan Native Other (please identify: Unknown
Patient's date of birth: (mm/dd/yy)
Age of patient at onset of symptoms:
Date of patient's initial symptoms: (mm/dd/yy)
Age of patient at time of death:
Patient's date of death: (mm/dd/yy)
Duration of illness: months
Was this case referred to the National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland, Ohio? yes no unknown
If yes, by whom was this case referred? Pathologist -- Neuropathologist -- Neurologist Other Physician (please identify which kind: Unknown
Who made initial diagnosis of CJD or other TSE?
Pathologist - Neuropathologist - Neurologist Other Physician (please identify which kind: ) Unknown
Please describe the clinical neurological presentation of the illness (list the symptoms or signs):
at onset of the illness:
during the course of illness:
Was an EEG (electroencephalogram) performed? yes -- no -- unknown
If yes,
how long after onset was the EEG performed?
how many times was the EEG performed?
can you indicate the results?
- slow periodic sharp waves (PSW)
- unilateral periodic sharp waves (LSW)
- not reported
- other
Was the cerebrospinal fluid tested for the 14-3-3 protein? yes - no - unknown
If yes, what was the result? positive - negative - unknown
Was a brain biopsy performed? - yes - no - unknown
If yes, what was the result?_____positive for____
______negative for CJD and other TSE's
______unknown
Was an autopsy performed? yes - no - unknown
If yes, what was the result? _____positive for____
______negative for CJD and other TSE's
______unknown
Was the neuropathology of this case consistent with new variant CJD? yes - no - unknown
* I hereby give consent to the Creutzfeldt-Jakob Disease Foundation, Inc. to use the above information, including name of patient if supplied, in connection with activities to promote the research, education and awareness of Creutzfeldt-Jakob Disease and related transmissible spongiform encephalopathies.
-4-
END ====================================================
NOW (below), compare to the CJD questionnaire _i_ propose for _all_ CJD/TSE victims/family in the USA;
A. What is the subjects SURNAME____________________________ B. What is the subjects status? ___________________________ (1=suspect/confirmed CJD, 2=hospital control (specify diagnosis), 3=GP control). C. If the subject is a (suspect) case, are they alive on the day of interview?_____(yes or no or not applicable) D. What is your (respondent's) name?_______________________ (first name, and surname) What is the relationship to (subject)?________________ address__________________phone________________________ E. DATE OF INTERVIEW__________________________ LOCATION OF INTERVIEW_____________________ F. NAME OF INTERVIEWER________________________
2. SUBJECT INFORMATION A. SEX___________________ B. BIRTH DATE____________ C. BIRTH PLACE___________ (country, state, county, city) D. ETHNIC ORIGIN_________ E. MARITAL*DOMESTIC STATUS__________________ (If the subject is female and is/has been married) record the subjects maiden name if different from current surname. F. PRESENT HOME ADDRESS_________________________ (ALSO, If deceased, last home address, before subject became ill?) G. Is/was subject right or left handed?__________________ F. How many years of full-time education?________________
3. PAST MEDICAL HISTORY A. Has the Subject had dental treatment other than fillings: e.g. extractions or root canal work?_________________ If yes, record a description of treatment; with dates; Dentists name and address____________________________ B. Has the Subject ever had any operations, including eye operations or stitching of wounds?___________________ (If yes, record the year, hospital and type of operation). _____________________________________________ _____________________________________________ _____________________________________________ (record total number of operations)
For each type of operation record the number of such operations undergone, the year of the first such operation and the year of the last such operation. When no such operations were undergone record 0 for the number of operations.
NEUROLOGIC (brain)_____________________________ EYE____________________________________________ ABDOMINAL______________________________________ ORTHOPEDIC_____________________________________ OTHER__________________________________________ TONSILS OUT?___________________________________ APPENDIX OUT?__________________________________ ever received an ORGAN TRANSPLANT, including corneal or bone marrow transplant?_____________________________________ kidney, liver, and other_______________________ C. BLOOD TRANSFUSION__________________________ TRANSFUSION OF ALBUMIN OR IMUNOGLOBULIN________ BLOOD DONOR____________________________________ D. Has Subject ever been admitted to a Hospital_______________________ E. Has Subject ever been to see psychiatrist (reason and treatment)_____________________
F. MEDICATIONS, has Subject taken any medications regularly, (if yes, record the date, name of the medication, the reason for taking it, and route of administration) prompt for prescription drugs, including insulin and type. _______________________________________________________ _______________________________________________________ _______________________________________________________ Prompt for hormone therapy or nutritional supplements including oral contraceptives and hormone replacement therapy: _______________________________________________________ _______________________________________________________ _______________________________________________________ Prompt for homeopathic/herbal therapy: _______________________________________________________ _______________________________________________________ _______________________________________________________ Prompt for eyedrops _______________________________________________________
SUMMARY OF ABOVE RESPONSES; HAS THE SUBJECT BEEN EXPOSED TO ONE OF THE MEDICATIONS OF BOVINE OR OVINE ORIGIN, AND OR ANY DESICCATED ANIMAL ORIGIN?
G. Has Subject ever been tested for allergy using needles?________________
H. Has Subject ever received a treatment involving a course of injections?_______________________________________________________ (If yes, record year, name of therapy, frequency, reason)
I. Has Subject been VACCINATED?_______________________________ (If yes, give name of vaccine, and route.)
J. Has Subject ever undergone lumbar puncture or electrical tests involving needles?________________________________________________
K. Has Subject ever undergone acupuncture?____________________
L. Has Subject ever used drugs by needle?_____________________
M. Has Subject ever been tattooed, ear or body piercing of anykind?______
4. FAMILY HISTORY PEDIGREE
(indicating years of birth and death) Subjects grandparents, Subjects parents and parents siblings, Subject and siblings Subjects children.
A. From the genealogy, record whether the Subject has been married more than once? ___________________________________________________
B. Have any of the BLOOD relatives of the Subject included in the Pedigree above died with dementia (or remain alive with dementia)?_________________________________________________________
C. Have any of these individuals been diagnosed as having Creutzfeldt-Jakob disease, and or any other T.S.E.?________________ (if so, give name, address, and apprx. date of illness)
D. CONFIRMATION OF FAMILY HISTORY OF CJD OR OTHER TSE'S
(1=definite 2=probable 3=possible 4=unable to confirm 5=not a case) _______________________________________________________________
E. Has Subject had social contact, through family, friends or work, with someone else who developed CJD?_____________________________ (record the persons name and the apprx. date of illness.)
F. Confirmation of social contact with case of CJD?____________
G. FOR NON-U.K. cases only, Has Subject lived in or visited the United Kingdom during the period 1980-1999?________________________ (if yes, record dat and duration of visits)
DIETARY HISTORY A. Has Subject ever been a vegetarian for a period of 1 year or more? (if yes), during what period was Subject vegetarian, and did the Subject eat any meat or fish at all during this time?______________
B. Does Subject have a history of any other dietary restrictions or eccentricities? (record apprx. dates and details of restrictions: _________________________________________________________ _________________________________________________________
C. How many years did Subject eat school dinners?__________________ (give dates)
D. Has the Subject ever eaten animal food or pet food?________________________________________________________ (If yes, record the types of food and dates)
E. How did/does the Subject like their steak cooked?________________
(1=well done 2=medium 3=medium-rare 4=rare 5=did not eat steak)
F. How often does/did Subject cut or chop up raw red meat or bones, in their work or in their home?_______________________________
G. (For each of the following food items) How often did Subject eat (food item)? BRAIN_________________(specify animal which organ came from) EYE___________________ TRIPE_________________ LIVER_________________ KIDNEY_______________ SWEETBREADS_________(pancreas) ROAST LAMB, LAMB COPS, LAMB STEW, ROAST PORK, HAM, BACON, ROAST BEEF, STEAK, BEEF STEW, MINCED BEEF, VEAL, VENISON, CHICKEN, BURGERS, MEAT PIES SUCH AS PORK, VEAL, AND HAM, STEAK AND KIDNEY, CHICKEN AND MUSHROOM, FAqqOTS, MEAT SAUSAGES, BLACK PUDDING, HAGGAS, LIVER SAUSAGE OR PATE', STEAK TARTARE (raw minced steak with raw egg) carpaccio, CHEESE, COWS MILK (1=drinks milk/eats breakfast cereal with milk, 2=only in tea/coffee, 3=NO)_______________________ ____________________________________________________________ ____________________________________________________________ ____________________________________________________________ ____________________________________________________________ ____________________________________________________________
5. EXPOSURE TO ANIMALS: A. Did the Subject every HUNT, DRESS, AND EAT, DEER____________________ ELK_____________________ SQUIRREL_______________ OTHER__________________ (if so, list location, and year, and list any specific organs that the Subject may have considered to be a delicacy).
B. Did the Subject share a home with: CATS________________ DOGS________________ FERRETS_____________
C. Has the Subject worked or stayed for more than one week on a farm? (1=lived or worked, 2=stayed, 3=NO) If YES, did Subject work or help with;
CATTLE______________ SHEEP________________ GOATS_______________ PIGS__________________ CHICKENS____________ MINK_________________ (If yes), did Subject participate in: Treating cattle for Warble fly?______________ Dipping sheep?_________________________ Crop Spraying?________________________ (If the Subject took part in any of these activities), record dates, places and details of the activity including agents used; ________________________________________________________ ________________________________________________________ ________________________________________________________
D. Has the Subject used any of the following; BONEMEAL__________________ HOOF AND HORN____________ DRIED BLOOD________________ MANURE____________________ (if yes, record the item used and dates)
E. Has Subject ever DISSECTED ANIMAL EYES, for example at school? _________________________________________________________
6. RESIDENTIAL HISTORY (begin with the most recent residence and work backwards) From(dd/mm/yy) TO(dd/mm/yy) STREET TOWN COUNTY STATE (include zip code). ________________________________________________________ ________________________________________________________ ________________________________________________________ ________________________________________________________ ________________________________________________________ ________________________________________________________ ________________________________________________________ ________________________________________________________
7. OCCUPATIONAL HISTORY OF SUBJECT; (begin with most recent occupation and work backwards) FROM(dd/mm/yy) TO(dd/mm/yy) NAME OF EMPLOYER TOWN DESCRIPTION OF WORK; _________________________________________________________ _________________________________________________________ _________________________________________________________ _________________________________________________________ _________________________________________________________ _________________________________________________________ _________________________________________________________
A. Has the Subject ever worked in farming, the meat industry, the pharmaceutical industry, or in a hospital?
B. Has the SUBJECT, their PARTNERS or PARENTS ever worked in the following areas;
medical/pharmaceutical/nursing/dentistry_____________________________ animal laboratories______________________________________________ pharmaceutical laboratories______________________________________ other research laboratories______________________________________ animal farming___________________________________________________ veterinary medicine______________________________________________ meat industry____________________________________________________ (BUTCHER'S/ABATTOIRS/RENDERING PLANTS, ETC) and or (catering other occupation involving animal products, including leather)? ______________________________________________________ ______________________________________________________ ______________________________________________________ ______________________________________________________ ______________________________________________________
*** NOTE ***
please include venison/sheep/lamb and the bovine to any of the above questions.
example=brain tanning deer/elk hide or any other topics that pertain to transmission of TSEs
_________________________________________________
example=antler velvet nutritional supplements
_________________________________________________
_any_ nutritional supplements??? name/ingredients
_________________________________________________
example=elk/deer brains ie/scrambled, sandwich or otherwise
_________________________________________________
COSMETICS-ie facial creams, eye make-up etc. name/brand/ingredients
MEDICAL-ENDOSCOPY WORK OF ANY TYPE __________________________________________________
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
=================================================== Greetings again Neurology,
snip...(snipped out repeated data/urls i posted again below)
Subject: Re: gutjnl_el;21 Terry S. Singeltary Sr. (3 Jun 2002) "CJDs (all human TSEs) and Endoscopy Equipment" Date: Thu, 20 Jun 2002 16:19:51 -0700 From: "Terry S. Singeltary Sr." To: Professor Michael Farthing CC: lcamp@BMJgroup.com References: <001501c21099$5c8bc620$7c58d182@mfacdean1.cent.gla.ac.uk>
Dear Gut,
snip...
here is my short submission i speak of, lengthy one to follow below that;
>> Date submitted: 3 Jun 2002 >> eLetter ID: gutjnl_el;21 >> >> Gut eLetter for Bramble and Ironside 50 (6): 888 >>----------------------------------------------------------------- >>Name: Terry S. Singeltary Sr. >>Email: flounder@wt.net >>Title/position: disabled {neck injury} >>Place of work: CJD WATCH >>IP address: 216.119.162.85 >>Hostname: 216-119-162-85.ipset44.wt.net >>Browser: Mozilla/5.0 (Windows; U; Win98; en-US; rv:0.9.4) >>Gecko/20011019 Netscape6/6.2 >> >>Parent ID: 50/6/888 >>Citation: >> Creutzfeldt-Jakob disease: implications for gastroenterology >> M G Bramble and J W Ironside >> Gut 2002; 50: 888-890 (Occasional viewpoint) >> http://www.gutjnl.com/cgi/content/abstract/50/6/888 >> http://www.gutjnl.com/cgi/content/full/50/6/888 >>----------------------------------------------------------------- >>"CJDs (all human TSEs) and Endoscopy Equipment" >>----------------------------------------------------------------- >> >>
regarding your article;
Creutzfeldt-Jakob disease: implications for gastroenterology
i belong to several support groups for victims and relatives of CJDs. several years ago i did a survey regarding endoscopy equipment and how many victims of CJDs have had any type of this procedure done. to my surprise, many victims had some kind of endoscopy work done on them. as this may not be a smoking gun, i think it should warrant a 'red flag' of sorts, especially since data now suggests a substantial TSE infectivity in the gut wall of species infected with TSEs. If such transmissions occur, the ramifications of spreading TSEs from endoscopy equipment to the general public would be horrible, and could potential amplify the transmission of TSEs through other surgical procedures in that persons life, due to long incubation and sub-clinical infection. Science to date, has well established transmission of sporadic CJDs with medical/surgical procedures.
Terry S. Singeltary Sr. CJD WATCH
# Docket No: 02-088-1 RE-Agricultural Bioterrorism Protection Act of 2002; [TSS SUBMISSION ON POTENTIAL FOR BSE/TSE & FMD 'SUITCASE BOMBS'] - TSS 1/27/03 (0)
Subject: 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 BSE-L
http://vegancowboy.org/TSS-part1of8.htm
#Docket No. 01-068-1 Risk Reduction Strategies for Potential BSE Pathways Involving Downer Cattle and Dead Stock of Cattle and Other Species - TSS 1/21/03 (2)
In Reply to: Docket No. 01-068-1 Risk Reduction Strategies for Potential BSE Pathways Involving Downer Cattle and Dead Stock of Cattle and Other Species [TSS SUBMISSION] January 21, 2003
Abnormal protein deposits were first recognised histologically in TSEs as amyloid plaques, which were found in the brains of some but not all models of the disease.
From: Nora.Hunter@netlink.co.nz To: tse-conference@netlink.co.nz Subject: TSE Conference: DIAGNOSTIC METHODS FOR TSEs (2) Sender: owner-tse-conference@netlink.co.nz
Diagnosis of TSEs by detecting abnormal forms of the host glycoprotein PrP
Robert A. Somerville Institute for Animal Health, Neuropathogenesis Unit, Edinburgh, Scotland, UK
[Submitted to the Electronic Conference on Surveillance for TSEs of Livestock, by Dr. N. Hunter, 13 May 1997]
PrP is a host-encoded glycoprotein, with Mr 25,000-34,000, depending on the degree of glycosylation. An abnormal form of this protein, designated PrPSc, accumulates in organs of animals infected with a TSE, notably in CNS tissues, but also (in some but not all cases) in lymphoid and other peripheral organs. PrPSc is thought to be specifically associated with TSE infection. There is controversy about its role: whether it comprises the agent (the protein-only or "prion" hypothesis), whether it is a component of the agent, or is solely a pathological product of infection.
Abnormal protein deposits were first recognised histologically in TSEs as amyloid plaques, which were found in the brains of some but not all models of the disease. Scrapie associated fibrils (SAF) were found by negative stain electron microscopy in extracts from all TSE infected brains examined. The fibrils are similar but not identical to other amyloid fibrils. They have been shown to be comprised of the protein PrP. Examination of brain extracts for SAF has been demonstrated to be a relatively effective although cumbersome method for diagnosing TSEs
Biochemical analysis has shown that the normal form of PrP (PrPC) can be distinguished operationally from the abnormal form (PrPSc) according to two criteria. PrPC is soluble in detergents whereas PrPSc sediments. PrPC is susceptible to protease digestion whereas PrPSc is partially resistant. These differences in properties may arise because PrP aggregates to produce the abnormal form.
Many antibody reagents have been developed which recognise PrP. A major problem in using them diagnostically is the need to discriminate between PrPC and PrPSc. It is necessary to apply at least one and preferably both operational criteria (i.e. the sedimentation and partial protease resistance of PrPSc) to discriminate between the two forms of the protein, before determining whether PrPSc is present in the test sample. Immunoblotting (Western blotting) of protein after resolution by SDS-PAGE has been preferred to dot blot or ELISA methodologies since specificity of detection by the antibody can be checked. However fewer samples can be processed. Immunohistochemical staining of tissue sections in our hands is of similar sensitivity to immunoblotting. It has the advantage of also providing anotomical detail of deposition, but processing of samples is more time consuming. It also depends on appropriate preservation of the tissue.
We have studied the deposition of PrPSc in experimental models of TSEs. PrPSc can be detected in brain, spleen, lymph nodes, pancreas and other organs. However the time at which PrPSc can be detected after infection in each organ varies according to various biological parameters, including strain of infecting agent, genotype of the infected animal and route of infection. In some models PrPSc could be detected in peripheral organs early after infection (e.g. 30 days after infection in a model with an incubation period of 170 days). However in other models PrPSc could not be detected until much later.
Interestingly in a murine model derived from BSE, PrPSc could only be detected in the spleen very late in the incubation period, if at all.
In ruminants PrPSc can be detected in brains of all clinically affected animals although sometimes the amounts are very small. PrPSc could also be detected in spleens of some sheep infected with scrapie but not in others; nor could it be detected in spleens from BSE infected cattle.
In conclusion, PrPSc detection, in particular post-mortem testing of brain, may sometimes be a useful adjunct to other methods of diagnosis, since tissue can readily be analysed for its presence. Indeed immunoblotting for PrPSc may be feasible on tissue samples where autolysis has occurred preventing other methods of diagnosis being applied, since the partial resistance of PrPSc to proteolysis prevents its degradation (if some tissue is frozen on autopsy and not all is fixed in formalin). However our failure to find PrPSc in spleens from BSE infected cattle, which correlates with the failure to detect infectivity in this and other peripheral organs, suggests that diagnosis for all TSEs based on sampling of peripheral organs may not be valid, since these organs may not accumulate PrPSc in all experimental or natural models of TSE.
"As implied in the Inset 25 we must _NOT_ assume that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease."
Subject: In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - REPORT OF A VISIT TO THE USA - APRIL-MAY 1989 - G A H Wells Date: Sat, 29 Jul 2000 18:38:04 -0700 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de
Perceptions of unconventional slow virus diseases of animals in the USA
G A H Wells
REPORT OF A VISIT TO THE USA
APRIL-MAY 1989
PAGE 1
Objectives
snip...
PAGE 25
Transmission Studies
Mule deer transmissions of CWD were by intracerebral inoculation and compared with natural cases resulted in a more rapidly progressive clinical disease with repeated episodes of synocopy ending in coma. One control animal became affected, it is believed through contamination of inoculam (?saline). Further CWD transmissions were carried out by Dick Marsh into ferret, mink and squirrel monkey. Transmission occurred in all of these species with the shortest incubation period in the ferret.
Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus ) Christina J. Sigurdson1, Elizabeth S. Williams2, Michael W. Miller3, Terry R. Spraker1,4, Katherine I. O'Rourke5 and Edward A. Hoover1
Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523- 1671, USA1 Department of Veterinary Sciences, University of Wyoming, 1174 Snowy Range Road, University of Wyoming, Laramie, WY 82070, USA 2 Colorado Division of Wildlife, Wildlife Research Center, 317 West Prospect Road, Fort Collins, CO 80526-2097, USA3 Colorado State University Veterinary Diagnostic Laboratory, 300 West Drake Road, Fort Collins, CO 80523-1671, USA4 Animal Disease Research Unit, Agricultural Research Service, US Department of Agriculture, 337 Bustad Hall, Washington State University, Pullman, WA 99164-7030, USA5
Author for correspondence: Edward Hoover.Fax +1 970 491 0523. e-mail ehoover@lamar.colostate.edu
Abstract
Mule deer fawns (Odocoileus hemionus) were inoculated orally with a brain homogenate prepared from mule deer with naturally occurring chronic wasting disease (CWD), a prion-induced transmissible spongiform encephalopathy. Fawns were necropsied and examined for PrP res, the abnormal prion protein isoform, at 10, 42, 53, 77, 78 and 80 days post-inoculation (p.i.) using an immunohistochemistry assay modified to enhance sensitivity. PrPres was detected in alimentary-tract-associated lymphoid tissues (one or more of the following: retropharyngeal lymph node, tonsil, Peyer's patch and ileocaecal lymph node) as early as 42 days p.i. and in all fawns examined thereafter (53 to 80 days p.i.). No PrPres staining was detected in lymphoid tissue of three control fawns receiving a control brain inoculum, nor was PrPres detectable in neural tissue of any fawn. PrPres-specific staining was markedly enhanced by sequential tissue treatment with formic acid, proteinase K and hydrated autoclaving prior to immunohistochemical staining with monoclonal antibody F89/160.1.5. These results indicate that CWD PrP res can be detected in lymphoid tissues draining the alimentary tract within a few weeks after oral exposure to infectious prions and may reflect the initial pathway of CWD infection in deer. The rapid infection of deer fawns following exposure by the most plausible natural route is consistent with the efficient horizontal transmission of CWD in nature and enables accelerated studies of transmission and pathogenesis in the native species.
Introduction
Chronic wasting disease (CWD) is a fatal prion disease affecting mule deer (Odocoileus hemionus), white-tailed deer ( Odocoileus virginianus) and Rocky Mountain elk (Cervus elaphus nelsoni). This transmissible spongiform encephalopathy (TSE) has been reported in captive and free-ranging deer and elk from north-eastern Colorado and south-eastern Wyoming (Spraker et al. , 1997 ; Williams & Young, 1980 , 1982 , 1992 ). Although the pathology of CWD is well- described (Williams & Young, 1993 ), little is known about CWD transmission. Epidemiological evidence from captive animals suggests that horizontal transmission may occur at a level apparently unparalleled in other prion diseases (Miller et al., 1998 ; Williams & Young, 1992 ). Other non- familial TSEs, such as kuru, transmissible mink encephalopathy and bovine spongiform encephalopathy (BSE) appear to be transmitted via ingestion of PrPres-infected tissue (Cervenakova et al. , 1998 ; Marsh & Bessen, 1993 ; Wells et al., 1998 ).
Few studies of early preclinical TSE infections have been performed in natural hosts or using probable natural routes of exposure; however, the results have been intriguing. BSE has been orally transmitted to cattle with infectivity detectable in the ileum of calves at 26 weeks post-inoculation (p.i.) (by mouse bioassay) (Wells et al., 1994 ). In another study, scrapie agent infectivity was first detected in the prescapular lymph nodes of goats at 24 weeks post- subcutaneous inoculation (Hadlow et al., 1974 ). However, mice inoculated intragastrically with scrapie had detectable infectivity in Peyer's patches and cervical lymph nodes as early as 1 week p.i. (Kimberlin & Walker, 1989 ). Thus, it appears that prions can cross the mucous membranes of the digestive tract to initiate infection in lymphoid tissue prior to invasion of the central nervous system and development of clinical disease.
Oral exposure is the most plausible pathway by which the CWD prion may be introduced to deer in nature. Consequently, we chose this means of inoculation in an attempt to demonstrate the feasibility of CWD transmission by this route and to study early lymphoid tissue tropism of the PrPres in deer. Each deer was repeatedly exposed to a known infectious CWD inoculum over a 5-day-period because recent results with scrapie in hamsters indicate repeated oral exposure increases the incidence of infection (Diringer et al., 1998 ). Because mice are relatively resistant to CWD (M. Bruce, personal communication) precluding bioassay, and because several studies have shown that PrPres strongly correlates with disease (McKinley et al., 1983 ; Race et al. , 1998 ), we employed an enhanced immunostaining method (formic acid, proteinase K and hydrated autoclaving) to detect PrPres in situ. Formic acid and hydrated autoclaving have been previously described for PrPres epitope exposure prior to immunohistochemistry (IHC) (Miller et al., 1994 ; van Keulen et al., 1995 ). Using these methods, we demonstrate PrPres in regional lymph nodes as early as 6 weeks after oral exposure of deer fawns to the CWD agent.
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Discussion
These results indicate that mule deer fawns develop detectable PrP res after oral exposure to an inoculum containing CWD prions. In the earliest post-exposure period, CWD PrPres was traced to the lymphoid tissues draining the oral and intestinal mucosa (i.e. the retropharyngeal lymph nodes, tonsil, ileal Peyer's patches and ileocaecal lymph nodes), which probably received the highest initial exposure to the inoculum. Hadlow et al. (1982) demonstrated scrapie agent in the tonsil, retropharyngeal and mesenteric lymph nodes, ileum and spleen in a 10-month-old naturally infected lamb by mouse bioassay. Eight of nine sheep had infectivity in the retropharyngeal lymph node. He concluded that the tissue distribution suggested primary infection via the gastrointestinal tract. The tissue distribution of PrPres in the early stages of infection in the fawns is strikingly similar to that seen in naturally infected sheep with scrapie. These findings support oral exposure as a natural route of CWD infection in deer and support oral inoculation as a reasonable exposure route for experimental studies of CWD.
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http://vir.sgmjournals.org/
Establishing the transmission of BSE to mink
44. Transmissible mink encephalopathy ("TME") is a rare disease of ranch reared mink, first recognised in the USA. It had been assumed to be scrapie in mink and, like BSE, outbreaks have epidemiological features consistent with a foodborne infection, but it has never been possible to demonstrate that scrapie infected sheep brain tissue is pathogenic to mink by oral exposure. In an incident of TME in Stetsonville, Wisconsin, USA in 1985 Dr Richard Marsh observed that although the rancher fed 'dead stock', mainly in the form of cattle carcasses, sheep tissues had never been fed. Studies in the USA of this incident showed not only that cattle inoculated intracerebrally with the mink brain developed a fatal spongiform encephalopathy, but also that the cattle passaged agent remained pathogenic for mink by either intracerebral inoculation or feeding. In the absence of reports of a clinical disease homologous to BSE in domestic cattle, these findings prompted the suggestion that a rare or occult form of such a disease might exist in the USA. Comparison of the biological properties of the BSE12 pathogen with those of the Stetsonville isolate was therefore of considerable interest in relation to hypotheses concerning possible origins of BSE and potential for subclinical infection in cattle. 45. Proposals to carry out studies with mink in the USA were developed in collaboration with, the United States Department of Agriculture ("USDA") Agricultural Research Service ("ARS") and the Department of Veterinary Science, University of Wisconsin, Madison, Wisconsin, USA. On 30th October, 1990 I attended a CVL/NPU BSE R&D meeting at the NPU in Edinburgh (YB90/10.30/1.1). I reported that brain material from BSE affected cows and a control cow (not fed meat and bonemeal) had been sent coded to Mr Mark Robinson (USDA) for transmission studies in mink. The studies were conducted from February 1991 under the control and principal funding of USDA-ARS. The results, discussed at the tenth CVL/NPU BSE R&D meeting on 27th April, 1993 (YB93/4.27/1.1) indicated that mink were indeed susceptible to BSE and, in contrast to previous attempts to transmit scrapie to the species, were susceptible by the oral route of inoculation. The collaboration resulted in the publication of a paper: Robinson, M.M. et al (1994) Experimental infection of mink with bovine spongiform encephalopathy. Journal of General Virology 75, 2151-2155 (J/JVIR /75/2151).
We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.
http://www.pnas.org/cgi/content/full/041490898v1
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
Subject: Re: hello Dr. Manuelidis...TSS ''BSE as another phenotype of sporadic CJD'' Date: Fri, 17 Jan 2003 17:38:00 -0500 From: laura manuelidis Reply-To: laura.manuelidis@yale.edu Organization: Yale University Medical School To: "Terry S. Singeltary Sr." References: <3E286F2F.6060700@wt.net>
Dear Terry,
Many thanks for the references, a rather late recognition of lots of experimental data that showed PrP was not predictive of disease. Nobody wanted to listen when I said years ago that vCJD should be able to transmit to people regardless of host PrP sequence differences. I also warned the CDC ~5 years ago that people infected by BSE strain might well show classic rather than vCJD lesions, and that their narrow sampling for vCJD by young age and PrP band pattern was based on preconceptions of Prion theory.
Additionally, Dickinson showed many years ago that scrapie could be subclinical in mice dying of old age, (and we showed transmissions of CJD that lacked PrP but had many vacuoles in the 1980s, also now conveniently ignored. Our Science paper further showed a typical sporadic CJD strain could evolve into one that provoked vCJD plaques. So really, there is not much new here except the authorship.
I also do not believe the glycosylation story since in 1987 we showed deglycosylation of PrP in infected brain samples yielded no differences from unglycosylated parallel samples in terms of incubation time, PrP band patterns or lesion profiles.
best, laura
"Terry S. Singeltary Sr." wrote:
> HI DOC, > > JUST read your (short abstract) of your latest > article; > > Unique inflammatory RNA profiles of microglia in Creutzfeldt-Jakob disease. > > then i got to wondering if you had read the new data > from Collinge et al? > > if not, i have posted below, with URL to go to full text. > i think this _should_ play a major factor to the medical/surgical > arena, but not to my surprize, nobody seems worried about > these new findings. well, new findings, but what i have > thought all along. i hope you find interest in this. > i would be please to know your thoughts on these findings, > they are very disturbing to me, but no media or medical > community has seemed to have picked up on it, and it's > not because i have not sent them the data;-) > > warmest regards, > terry > > Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD > Date: Thu, 28 Nov 2002 10:23:43 -0000 > From: "Asante, Emmanuel A" > To: "'flounder@wt.net'" > > Dear Terry, > > I have been asked by Professor Collinge to respond to your > request. I am a Senior Scientist in the MRC Prion Unit and the lead > author on the paper. I have attached a pdf copy of the paper for your > attention. Thank you for your interest in the paper. > > In respect of your first question, the simple answer is, yes. As you > will find in the paper, we have managed to associate the alternate > phenotype to type 2 PrPSc, the commonest sporadic CJD. > > It is too early to be able to claim any further sub-classification in > respect of Heidenhain variant CJD or Vicky Rimmer's version. It will > take further studies, which are on-going, to establish if there are > sub-types to our initial finding which we are now reporting. The main > point of the paper is that, as well as leading to the expected new > variant CJD phenotype, BSE transmission to the 129-methionine genotype > can lead to an alternate phenotype which is indistinguishable from type > 2 PrPSc. > > I hope reading the paper will enlighten you more on the subject. If I > can be of any further assistance please to not hesitate to ask. Best wishes. > > Emmanuel Asante > > <> > ____________________________________ > > Dr. Emmanuel A Asante > MRC Prion Unit & Neurogenetics Dept. > Imperial College School of Medicine (St. Mary's) > Norfolk Place, LONDON W2 1PG > Tel: +44 (0)20 7594 3794 > Fax: +44 (0)20 7706 3272 > > PLEASE SEE FULL TEXT OF THIS ARTICLE; > > http://www.vegsource.com/talk/madcow/messages/9912118.html
Thank you for your stimulating message. John Collinge's paper, as usual, is provocative but also confusing as his infected Tg mice show a tremendous variability in incubation times from inoculum to inoculum which is puzzling. Unfortunately, John Collinge continues to use confusing terminology that is different from that proposed by us and endorsed by most groups around the world. The subtype of sporadic CJD that Collinge calls type 129 MM 2 is the one that we call 129 MM (MV) type 1 while your son, Jeffrey had sCJD MM2 which Collinge calls our SCJD MM2 129 MM type 3. I know it is very confusing, but the bottom line in that we our diagnosis on Jeffrey is different from the CJD subtype Collinge reports in his publication.
We are working on further characterization of our sCJD MM2 cortical. I enclose a reprint of one of our recent publications on this subject. Also, on behalf of the National Prion Disease Pathology Surveillance Center, I thank your for your support and interest.
Best regards, Pierluigi Gambetti, M.D. ---------------------------- =============================================================== how can three very well known and respected TSE Scientist be on totally seperate pages in regards with sporadic CJDs? how is it with all these _documented_ animal TSEs in the USA, the fact they all transmit to primates, with the unknown of BSE/TSE in USA cattle (except Dr. Marsh did prove some TSE was in USA cattle), and sporadic CJD and Alzheimer's increasing in the USA, with Asante/Collinge et al new/old findings, how is it all sporadic CJD in the USA are just a happen-stance of bad luck or spontaneous happening of some sort $$$
now, why i have said all along we must keep the lobbyist and politicians (same thing), far away from scientific matters, especially human/animal TSEs, with there ties to some many Industries $
Subject: Re: TSE's blood test Date: Tue, 27 Jun 2000 21:30:13 -0500 From: "Mary Jo Schmerr" To:
Dear Mr. Singeltary,
I am very sorry about the terrible death that your mother had to endure. Stories like this keep me motivated to continue in my research. We are collaborating with scientists working on the human side and the results are very promising. We could move much faster, I believe, if we had more resources and if I received much stronger support from my administrators. It seems that many artificial roadblocks are placed in front of me. I appreciate your interest and support of the research that I do. Hopefully, we will get to a test soon.
Best wishes, Mary Jo Schmerr
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Subject: Re: hello Dr. Schmerr Date: Wed, 25 Dec 2002 16:08:03 -0600 From: "Mary Jo Schmerr" To:
Dear Mr. Singeltary,
Thanks for your comments.
Best, Mary Jo
>>> "Terry S. Singeltary Sr." 12/17/02 11:16 AM >>> re-if we had more resources and if I received much stronger support from my administrators. It seems that many artificial roadblocks are placed in front of me....
bet those roadblocks won't be so difficult now;-)
Subject: IT'S A SLAM DUNK FOR DR. SCHMERR AND HER MAD COW TEST $1.3 MILLION AWARDED "her bosses held back her research and related presentations." Date: Tue, 17 Dec 2002 10:29:11 -0600 From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy To: BSE-L@uni-karlsruhe.de
A USDA researcher in Ames filed a lawsuit claiming her bosses had retaliated against her.
By PERRY BEEMAN Register Staff Writer 12/17/2002 A federal jury Monday awarded $1.3 million to an Ames-based U.S. Department of Agriculture researcher who accused her bosses of retaliating against her for a gender discrimination complaint that led to the lawsuit.
Mary Jo Schmerr, a research chemist at the USDA National Animal Disease Center, had gained notoriety for developing a test for mad cow disease. Her bosses questioned whether the test worked and wouldn't let her travel to conferences to report her findings.
Schmerr contended she was treated badly when she complained about the<
