Friday, December 30, 2011

Detection of central nervous system tissue as bovine spongiform encephalopathy specified risk material in traditional Turkish meat products, farmers, and sporadic CJD in Turkey

Research Article

Detection of central nervous system tissue as bovine spongiform encephalopathy specified risk material in traditional Turkish meat products

Mehmet Kale1,*,

Sibel Hasırcıoglu1,

Cagdas Ozturk2,

A Selcen Akcan Kale3,

Yusuf Dogruer4

Article first published online: 22 DEC 2011

DOI: 10.1002/jsfa.5527

Copyright © 2011 Society of Chemical Industry

Keywords:CNS;BSE-SRM;Turkish meat products;ELISA


BACKGROUND: This study used enzyme-linked immunosorbent assay kits to investigate the presence of central nervous system (CNS) tissue in commercial raw and processed traditional Turkish meat products offered for consumption in various markets.

RESULTS: Ninety-six raw traditional Turkish meat products (32 fresh raw beef patties, 32 cig kofta, 32 pastirma) and 64 processed traditional Turkish meat products (32 doner kebabs and 32 fresh processed beef patties) were analysed. CNS tissue was not found in pastirma, doner kebab, or fresh processed beef patty samples. The levels of CNS contamination in fresh raw beef patties were low (0.1% absorbance standard; 3.1%) and moderate (0.2% absorbance standard; 6.2%). The level of contamination in the cig kofta was low (0.1% absorbance standard; 18.8%).

CONCLUSION: CNS tissue was present in all raw traditional Turkish meat products except for pastirma. Copyright © 2011 Society of Chemical Industry



where did they ship those SRM beef patties too ???


what’s the history with those farmers ???

5 out of 9 sporadic CJD victims farmers ???

another coincidence $$$

From: TSS

Subject: Increased incidence of sporadic CJD on the island of Crete

Date: August 3, 2001 at 7:28 pm PST

Increased incidence of sporadic Creutzfeldt-Jakob disease on the island of Crete associated with a high rate of PRNP 129-methionine homozygosity in the local population

Andreas Plaitakis, MD 1 *, Anna K. Viskadouraki, MD 1, Minas Tzagournissakis, MD 1, Ioannis Zaganas, MD 1, Susan Verghese-Nikolakaki, PhD 2, Vasilis Karagiorgis 2, Ioannis Panagiotides, MD 3, Constantine Kilindireas, MD 4, Eustratios Patsouris, MD 5, Christine Haberler, MD 6, Herbert Budka, MD 6, Theodoros Sklaviadis, PhD 2 1Department of Neurology, Division of Medicine, University of Crete, School of Health Sciences, Heraklion, Crete, Greece 2Laboratory of Pharmacology, Department of Pharmaceutical Sciences, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece 3Department of Pathology, Division of Medicine, University of Crete, School of Health Sciences, Heraklion, Crete, Greece 4Department of Neurology, University of Athens, School of Medicine, Athens, Greece 5Department of Pathology, University of Athens, School of Medicine, Athens, Greece 6Institute of Neurology, University of Vienna, Vienna, Austria email: Andreas Plaitakis (

*Correspondence to Andreas Plaitakis, Department of Neurology, University of Crete, School of Health Sciences, Voutes, Heraklion, Crete, Greece

Funded by: General Secretariat of Research and Technology of Greece; Grant Number: YPER-97 Association for the Advancement of Research and Treatment of Neurologic Disorders of Crete Eú Zr


Since the spring of 1997, when the Neurology Department of the University Hospital of Crete admitted its first patient, 9 cases (8 neuropathologically confirmed and 1 probable) of sporadic Creutzfeldt-Jakob disease (sCJD) have been recorded. This represents an annual incidence five-fold higher than expected based on the island's population (0.54 million). Molecular analysis of the prion-protein gene (PRNP) showed no mutations in any of the seven CJD cases studied. Five patients (ages 64-88 years) were homozygous for methionine-129 of PRNP and showed the classic sCJD triad (subacute dementia, myoclonus, periodic electroencephalogram). Brains contained Type 1 (unglycosylated 21.5 kDa band) protease-resistant prion protein (PrPres). Two patients (ages 56 and 57 years), both homozygous for valine-129, showed cerebellar ataxia and later dementia not associated with periodic electroencephalogram; brain PrPres was Type 2. Genotyping of 205 Cretan controls showed that methionine-129 homozygosity, a susceptibility factor for sCJD, was significantly higher in this population than in other Caucasian populations (57.0%, n = 205 versus 41.5%, n = 859. These data are the first to relate a high regional incidence rate for sCJD to the distribution of PRNP 129 genotypes in the local population; however, additional factors may be operational.

Received: 11 December 2000; Revised: 3 April 2001; Accepted: 3 April 2001

Distribution of the M129V polymorphism of the prion protein gene in a Turkish population suggests a high risk for Creutzfeldt-Jakob disease

Nihan Erginel-Unaltuna1, Katell Peoc'h2, Evrim Komurcu1, Tufan Tevfik Acuner3, Halim Issever4 and Jean-Louis Laplanche*,2 1Department of Genetics, Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey; 2Service de Biochimie et Biologie MoleÂculaire, Association Claude Bernard, HoÃpital LariboisieÁre, Paris, France; 33rd Neurology Clinic, Turkish Ministry of Health Bakirkoy Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey; 4Division of Biostatistics and Demography, Department of Public Health, Istanbul Medical School, Istanbul University, Istanbul, Turkey

A polymorphism (M129V) at codon 129 of the prion protein gene (PRNP) results in either a methionine residue (Met) or a valine residue (Val) and is known to determine susceptibility for the development of sporadic or acquired Creutzfeldt-Jakob disease (CJD). The distributions of M129V genotypes and alleles in various general populations have been reported and there are clear differences between Western Europeans and East Asians. We analysed the coding sequence of the PRNP gene in 100 healthy Turkish subjects to determine whether the distributions of the M129V genotypes and alleles or other PRNP gene variants in the Turkish population differ from those in other normal populations. Three known polymorphisms but no other gene variants were detected in the PRNP coding sequence of the Turkish individuals. Genotype frequencies at codon 129 were 57% Met/Met, 34% Met/Val and 9% Val/Val, with an allele frequency of 0.740 : 0.260 Met:Val. These distributions are considerably different from those reported for other normal populations residing in Western Europe and East Asia, except in Crete. The higher frequency of 129 Met-homozygotes in Turkey than in Western Europe suggests that the Turkish are at greater risk of developing CJD.

European Journal of Human Genetics (2001) 9, 965 ± 968.

Keywords: Creutzfeldt-Jakob disease; prion; gene; PRNP; polymorphism; Turkey; population; genetic


Consequently, the distributions of the M129V genotypes and alleles in the Turkish population differ considerably from those reported for other normal populations residing in either Western Europe or East Asia, with the notable exception of Cretan natives. A recent report19 found that the high rate of PRNP 129Met homozygosity in Crete was associated with a local increase in the incidence of sporadic CJD. As homozygosity at PRNP codon 129 is a recognized risk factor for sporadic and acquired CJD in Caucasians5,21 and heterozygosity is protective,2 ± 4,21 the higher frequency of 129Met-homozygotes in Turkey than in Western Europe would also suggest that the Turkish are at increased risk of developing CJD.

Increased Incidence of Sporadic Creutzfeldt- Jakob Disease on the Island of Crete Associated with a High Rate of PRNP 129-Methionine Homozygosity in the Local Population

Andreas Plaitakis, MD,1 Anna K. Viskadouraki, MD,1 Minas Tzagournissakis, MD,1 Ioannis Zaganas, MD,1 Susan Verghese-Nikolakaki, PhD,2 Vasilis Karagiorgis,2 Ioannis Panagiotides, MD,3 Constantine Kilindireas, MD,4 Eustratios Patsouris, MD,5 Christine Haberler, MD,6 Herbert Budka, MD,6 and Theodoros Sklaviadis, PhD2

Since the spring of 1997, when the Neurology Department of the University Hospital of Crete admitted its first patient, nine cases (eight neuropathologically confirmed and one probable) of sporadic Creutzfeldt-Jakob disease (sCJD) have been recorded. This represents an annual incidence five-fold higher than expected based on the island’s population (0.54 million). Molecular analysis of the prion-protein gene (PRNP) showed no mutations in any of the seven CJD cases studied. Five patients (ages 64–88 years) were homozygous for methionine-129 of PRNP and showed the classic sCJD triad (subacute dementia, myoclonus, periodic electroencephalogram). Brains contained type 1 (unglycosylated 21.5 kDa band) protease-resistant prion protein (PrPres). Two patients (ages 56 and 57 years), both homozygous for valine-129, showed cerebellar ataxia and later dementia not associated with periodic electroencephalogram; brain PrPres was type 2. Genotyping of 205 Cretan controls showed that methionine-129 homozygosity, a susceptibility factor for sCJD, was significantly higher in this population than in other Caucasian populations (57.0% n 5 205 vs. 41.5% n 5 859, p < 0.0001). These data are the first to relate a high regional incidence rate for sCJD to the distribution of PRNP 129 genotypes in the local population; however, additional factors may be operational.

Ann Neurol 2001;50:227–233


Table 1. Demographic and Clinical Features of Creutzfeldt-Jakob Disease Cases

Number Age (yrs)/ Gender Occupation Presenting Symptoms Neurological Features Hospital Course

1 56/M Electrician Severe gait ataxia, photophobia, nervousness for 2–3 months Profound cerebellar-oculomotor deficits, mild cognitive decline Rapid neurological decline, death in 2 months

2 57/M Post office employee Gait disturbances, mild memory loss for 2 months Cerebellar and extrapyramidal syndrome, mild cognitive decline Rapid neurological decline, death in 2 months

3 76/M Farmer Visual illusions, mental changes for 1 month Profound dementia, mutism, myoclonus, head scratching Rapid decline, coma in 2 months, death in 7 months

4 68/F Farmer Depression, emotional lability for 2 months Profound dementia, visual hallucinations, myoclonus, ataxia Rapid neurological decline, death in 2.5 months

5 88/M Farmer Mental changes for 1 month Profound dementia, visual hallucinations, myoclonus, ataxia Rapid neurological decline, death in 5 weeks

6 81/F Housewife Insomnia, irritability for 1 year, memory loss for 2 months Profound amnesia, myoclonus, akinetic mutism Rapid neurological decline, death in 2 weeks

7 64/M Restaurant owner Dizziness, unsteadiness, mental changes for 1 month Profound dementia, movement disorder, myoclonus, seizures Rapid neurological decline, death in 4 months

8 65/M Farmer Dizziness, gait disturbances, mental changes for 1.5 months Profound dementia, myoclonus, akinetic mutism Rapid neurological decline, death in 2 months

9 65/F Farmer Distorted vision, hallucinations, mental changes for 2 months Profound dementia, myoclonus, hypertonus, visual hallucinations Rapid neurological decline, death in 2 weeks



During the past three and a half years, the annual incidence of sCJD on Crete was 4.76 cases per million. This is about five times greater than annual mortality rates recorded in recent years in several European countries as well as the United States. Although the population of Crete has a high life expectancy,12 this does not appear to be a major factor since age-specific and age-adjusted incidence rates were four- to ten-fold greater than reported elsewhere. To our knowledge, CJD had not been previously recorded on Crete, but a Neurology Department did not exist on the island until 1997. Hence, it is unclear if the epidemiology of the disease has changed recently in this region. Because the reporting period is relatively short, long-term data are needed to see whether the incidence rates recorded here persist or change over more extended periods of observation.

The increased incidence of CJD on Crete is not due to familial cases of the disease in the island’s population. None of our cases had a positive family history, and analysis of the coding region of the PRNP failed to detect mutations associated with familial CJD. We cannot exclude the possibility of DNA changes outside of the coding region of the PRNP studied here, but no such changes predisposing to CJD are currently known.

known. We observed two distinct phenotypes of CJD. The first was seen in seven patients, 64–88 years of age, who showed the classic sCJD triad of rapidly advancing dementia, myoclonic jerks, and periodic sharp waves on EEG. Five of these were tested and found to be homozygous for Met129 of PRNP. Brains showed accumulation of type 1 PrPres (unglycosylated 21.5 kDa band), as defined by Parchi et al.10 The second phenotype was seen in two patients, 55 and 57 years of age, who showed cerebellar ataxia and later dementia in the absence of periodic EEG changes. Both were homozygous for Val129 and their PrPres (unglycosylated band 21.5 kDa)10 was type 2. These findings are in accordance with those of recent reports13,14 showing that codon 129 polymorphism influences the clinical expression of sCJD.

snip... see full text ;

Case Report Creutzfeldt-Jacob Disease: a case report Eren Gozke1,2*, Nursel Erdal1,2 and Muge Unal1,2

* Corresponding author: Eren Gozke

Author Affiliations

1 Department of Neurology, FSM Teaching and Research Hospital, Istanbul, Turkey

2 Fatih Sultan Mehmet Egitim ve Arastirma Hastanesi, E-5 üzeri, Bostanci, Istanbul, Turkey

For all author emails, please log on.

Cases Journal 2008, 1:146 doi:10.1186/1757-1626-1-146

The electronic version of this article is the complete one and can be found online at:

Received: 9 July 2008 Accepted: 9 September 2008 Published: 9 September 2008

© 2008 Gozke et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Introduction Creutzfeldt-Jacob Disease is the most frequently seen type of prion diseases. Its clinical findings consist of predominantly progressive dementia with a rapid onset, myoclonus, and also cerebellar, pyramidal, extrapyramidal and visual signs. Definitive diagnosis is established with histological examination of brain biopsy or autopsy materials. Occurrence of periodical spikes in EEG, observation of cortical signal alterations during diffusion weighted (DW) MRI studies, and detection of protein 14-3-3 in cerebrospinal fluid (CSF) substantiate the diagnosis.

Case presentation Seventy year-old male patient referred with complaints of weakness and involuntary movements in left arm, changes in behavior, and forgetfulness. He also developed akinetic mutism after nearly three months. In EEG periodic triphasic waves were seen. Despite the absence of any apparent pathological finding in T2 and FLAIR MRI, excluding signs of atrophy, on DW MRI hyperintense signal changes in cortical regions (cortical ribboning) were observed. Protein 14-3-3 in CSF was detected.

Conclusion Patients who have progressive dementia and associated atypical features should be investigated especially with DW MRI. Cortical ribboning is a very useful diagnostic sign for CJD.


Case presentation Three months before referral to our clinics, this 70 year-old patient experienced complaints such as difficulty in raising 3rd and 4th digits of his hands, insomnia, irritability, inability to find his way home. In cranial MRI bilateral cerebral cortical atrophy more prominent on the frontoparietal region was detected. The condition was evaluated as Alzheimer type dementia and cholinesterase inhibitors were initiated. To exclude the diagnosis of cervical radiculopathy and motor neuron disease, he underwent cervical MRI and EMG without detection of any specific finding. Two months after the onset of his complaints, visual hallucinations and tremor of the right hand were added. Cranial MRI was repeated without any detection of change. One month later neurologic examination revealed a mild degree of cognitive deficit, cerebellar signs in the right upper extremity and apraxia. The patient denied hospitalization for follow-up. Within ten days insomnia, irritability and agitation emerged, and he experienced delusions of being killed by their relatives, his speech became unintelligible and his gait instable. He was admitted to the hospital after a generalized tonic-clonic seizure. Neurological examination revealed drowsiness and disorientation. Facial asymmetry was absent, and extraocular movements were intact. Pupils were isochoric and at the midline with normal direct and indirect light reflexes. He was moving all his extremities in response to painful stimuli. Postural and action tremors and diffuse myoclonus emerging spontaneously and response to auditory or tactile stimuli were observed. Deep tendon reflexes were diminished, and planter reflexes were irrelevant bilaterally. Speech was extremely dysarthric and difficulty in swallowing was noted. Past medical history was unremarkable. Any abnormality besides lower TSH levels in laboratory tests could not be detected. From the 3rd day of his hospitalization akinetic mutism developed. EEG showed 4–5 cps teta waves in background activity and also slow triphasic waves with higher amplitude on frontal regions were detected. In differential diagnosis Hashimoto encephalitis was contemplated secondary to lower levels of TSH. Laboratory findings of the patient were interpreted as subclinical hyperthyrodism. Marked cerebral atrophy in frontoparietal regions and several ischemic-gliotic foci were seen on cranial MRI, T2 weighted and FLAIR imaging, while hyperintense areas (cortical ribboning) all over the cortex was noted in DW MRI (Figure 1). Any increase in signal intensity was not detected in putamen and caudate nucleus. In CSF examination protein, glucose and electrolyte levels were within normal limits and no cell seen. However 14-3-3 protein was positive. Patient diagnosed as sporadic CJD and died within 4 months after the onset of his complaints.




Opinion of the Scientific Steering Committee on the GEOGRAPHICAL RISK OF BOVINE SPONGIFORM ENCEPHALOPATHY (GBR) in Turkey Adopted by the SSC on 27 June 2002


THE ANALYSIS EXTERNAL CHALLENGE The level of the external challenge that has to be met by the BSE/cattle system is estimated according to the guidance given by the SSC in its final opinion on the GBR of July 2000 (as updated in January 2002). Live cattle imports: In total the country imported over the period 1980-2001 more than 1.1 million live cattle from BSE-risk countries, of which 929 came from the UK. Most of these cattle were imported for immediate slaughter or fattening but overall these imports represent a very high external challenge. Broken down to 5-years periods the resulting external challenge resulting from live cattle imports was very low from 1980-1985, high from 1986 to 1990, very high from 1991-1995 and high thereafter. This assessment takes into account all aspects that allow assuming that certain imported cattle did not enter the domestic BSE/cattle system, i.e. were not rendered into feed, while approaching the end of the BSE-incubation period. MBM imports: In total the country imported over the period 1980 to 2001 more than 65.000 tons of MBM from BSE-risk countries but nothing from the UK. The claim that 90% of these imports were fishmeal or non-mammalian MBM was not substantiated. Together these imports are therefore assumed to represent a very high external challenge. Broken down to 5-years periods the resulting external challenge was high from 1980-1985, very high from 1986-1990, and moderate thereafter. This assessment takes into account all aspects that allow assuming that certain imported MBM did not represent an external challenge. STABILITY On the basis of the available information it was concluded that the country’s BSE/cattle system was very unstable from 1980 to 1995 and has been unstable since 1996/97. Feeding Until a feed ban was adopted in 1996/97, feeding MBM to ruminants was legally possible. Therefore feeding is assessed as "not OK" before 1997. Controls of the 1997-feed ban are in place since 1997 and feeding is regarded “reasonably OK” since 1996/97. Rendering Rendering was and is common practise in Turkey. SRM appear to be potentially included in the rendering but fallen stock is excluded. The process conditions seem to be generally appropriate but cannot be fully assessed as evidence for these and for controls is not supplied. Rendering is assessed as "reasonably OK" throughout the reference period. SRM-removal There is no SRM ban. While fallen stock is apparently not rendered it cannot be excluded that SRM entered/enters rendering. SRM removal is therefore assessed as “not OK” throughout the reference period. Scientific Steering Committee – Opinion on the GBR of TURKEY June 2002 - 4 - BSE surveillance Passive BSE surveillance existed since some time but BSE only became notifiable in 1997. Active surveillance has begun in June 2001 but this is not yet regarded to be sufficient to detect low levels of BSE-incidence. CONCLUSION ON THE CURRENT GBR The very unstable BSE/cattle system of Turkey was exposed to a high and very high external challenge since the early 80s. It is therefore likely that the BSE agent was introduced into the country and recycled and amplified. As the system is still regarded to be unstable it is concluded that it is likely but not confirmed that one or several domestic cattle are (pre-clinically or clinically) infected with the BSE-agent (GBR III). EXPECTED DEVELOPMENT OF THE GBR As long as the stability remains as low as it is, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent will increase, also without any further external challenge.


NO Scrapie cases in Turkey ???

Distribution of risk groups in Turkish native sheep breeds for classical scrapie and atypical scrapie

all this sounds very familiar to me ;

Monday, May 19, 2008


‘The first farmer’ – August 1992

5.7 At the beginning of August 1992, Dr Will confidentially informed Dr Ailsa Wight (DH, senior medical officer with responsibility for TSEs), that a probable case of CJD had occurred in a 60-year-old farmer whose farm, in the Manchester area, had a history of BSE. Dr Wight passed on this information to Sir Kenneth Calman (CMO) on 13 August 1992, stating that the CJD patient was alive and had been visited by the CJDSU.188 Although unconfirmed, the diagnosis was considered likely to be CJD on clinical grounds. Dr Wight advised that: There is no direct evidence that the two events (BSE and CJD) are linked and Dr Will feels they are probably a coincidence. Despite the rarity of CJD, it was perhaps only a matter of time before this situation arose, given the large numbers of people employed in the agricultural and related industries, and the fact that BSE cases now total over 65,000.189

5.8 This ‘first case’ of CJD in a cattle farmer was discussed by SEAC190 at their 13th meeting on 15 October 1992.191 Dr Will informed the meeting that one of the farmer’s cows had confirmed BSE in 1989 and that the farmer had developed CJD two years later.192

5.9 Dr Will informed SEAC that he intended to publish a report of his study of this case in a scientific journal ‘which would probably draw the conclusion that there was no evidence that this was not a chance occurrence of normal disease’. Dr Will also reported that his studies at the CJDSU had failed to reveal a correlation between occupational backgrounds and CJD to date.193

5.10 On 22 October 1992, a minute from Mr Thomas Murray (SEAC DH Secretariat) informed the Secretary of State about the SEAC meeting and the fact that the farmer had now died.194 He noted that the diagnosis of CJD had been confirmed by pathology and that the CJDSU had also ruled out iatrogenic or familial CJD, as well as exposure to cattle brain. He commented that the SEAC meeting had come ‘to the view that all indications suggested that it was a typical sporadic case of CJD. However in view of the history it is hoped to carry out further laboratory studies to try to confirm this.’ 185

YB89/10.26/3.1 186 YB89/10.26/3.2 187 YB89/11.20/11.1 188 YB92/8.13/2.1–2.2 189 YB92/8.13/2.1–2.2 190

SEAC – Spongiform Encephalopathy Advisory Committee. This Committee was set up after advice from the Tyrrell Committee. Dr Will was a member of SEAC from its outset 191

YB92/10.15/2.1–2.8 192 YB92/10.15/2.4 193 YB92/10.15/2.4 194 YB/92/10.22/1.1–1.2


Dr Will published his report of the case, ‘Creutzfeldt-Jakob Disease in an Individual Occupationally Exposed to BSE’, as a letter in The Lancet on 6 March 1993.195 The letter concluded that ‘CJD in our case is most likely to have been a chance finding and a causal link with BSE is at most conjectural’. The letter noted that the only possible direct route of cross-contamination was that the farmer had drunk pooled milk from his herd which included that from the affected cow, but that epidemiological evidence had largely precluded milk as a route of transmission in spongiform encephalopathies.

5.12 This letter created much media interest over the following few days, and its contents were reported in The Times,196 Today,197 Daily Express,198 Daily Mail,199 and Daily Telegraph which also reported Mr Kevin Taylor (Assistant Chief Veterinary Officer, MAFF) stating ‘I don’t think that a link between this case and BSE is even conjectural’ and rejecting fears that the farmer might have contracted the illness from milk.200

5.13 On 10 March 1993, Mr Jimmy Young of BBC Radio 2, interviewed microbiologist Professor Richard Lacey, who commented that: The good news is that this farmer, I think, got it too soon. If BSE produces this disease in people it will take, perhaps, another 5 or 10 years. So I think this is a one-off coincidence and I don’t think this farmer got his disease, CJD, from BSE. But nevertheless the underlying worries remain and I think it’s reasonable that this issue should be discussed. 201

5.14 The Second Annual Report of the CJDSU, published in July 1993, concluded that: 202 This is most likely to have been a chance occurrence rather than indicating any causal link with BSE.

5.15 It further noted that: A farmer’s wife who was diagnosed in 1992 had worked on a small holding for over 20 years but there had not been a case of BSE in the herd (Wilesmith, Personal Communication).203


‘The second farmer’ – July 1993

5.16 In early July 1993, Dr Will informed DH of a ‘second’ case of CJD in a farmer with BSE in his herd. The diagnosis had been confirmed by brain biopsy.204

5.17 Dr Wight described the case in a minute sent on 12 July 1993 to the private secretaries to Baroness Cumberlege and Sir Kenneth Calman. The minute was copied to others in DH and to Mr Howard of MAFF. The 64-year-old dairy farmer from the West Country was thought to have had at least two BSE cases in his herd, which were diagnosed in 1992. He was also thought to have assisted in calving and to have drunk the milk from his herd. His clinical symptoms had begun in May 1993. She commented that the history did not suggest anything other than a sporadic case of CJD but that DH was taking expert advice on the case.205

5.18 On 19 July 1993, Mr Kevin Taylor (MAFF) minuted the private secretary to Mrs Gillian Shephard, the MAFF Minister, in a response to a request for more detailed briefing.206 He noted that neither Dr Will nor the CJDSU intended to publicise the case at that time unless it attracted media attention, as they intended to include the information in their Third Annual Report due in approximately one year, ie, July 1994.

5.19 The minute attached a briefing note for the Minister. This specifically mentioned the consideration of occupational exposure to BSE as discussed in the CJDSU’s Second Annual Report which concluded that: . . . current information does not suggest that occupation is linked to an increased risk of developing CJD and it includes occupations which might involve an increased exposure to the agent of BSE.207

5.20 On 20 July 1993, SEAC held a meeting to consider this ‘second case’.208 They decided that a connection between occupation and CJD was unlikely and no conclusions could be drawn from the available statistical information. A paper by Professor Smith was presented which concluded that ‘the observation of two cases in workers in dairy farms with BSE-infected herds is disquieting, but the evidence is insufficient at this stage to draw any definite conclusions’.209

5.21 On 12 August 1993, the Daily Mail and Today publicised the story of the ‘second case’ of CJD in a dairy farmer.210 Both named the farmer and reported a DH spokesman saying that the Government’s experts had considered the case and ‘agreed that there are no features that give cause for undue concern’. The spokesman had also commented that it was most unlikely that there was any direct link between BSE and CJD in the patient.

5.22 In September 1993, the case study of this ‘second farmer’ was published in The Lancet. This letter gave the farmer’s age as 54.211 204

YB93/7.12/1.1 205 YB93/7.12/1.1 206 YB93/7.19/1.1 207 IBD2 tab 6 p. 6 208 YB93/7.20/1.1 209 YB93/7.20/1.5 210 YB93/8.12/1.3–1.4 211 Davies, P.T., Jahfar, S., Ferguson, I.T. and Windl, O. (1993) Creutzfeldt-Jakob Disease in an Individual Occupationally Exposed to BSE, The Lancet, 342, 680


Her note had a separate heading for ‘Comparison with young onset cases in world literature’. Here she noted that Creutzfeldt’s first patient was 23 years old (reported in 1920), and that there were other cases of CJD in young people which predated the emergence of BSE. These were a 20-year-old female and a 16-year-old female in the US and a 19-year-old female in France.219


‘The third farmer’ – December 1994

5.33 A ‘third case’ associated with farming where cattle in the herd had contracted BSE concerned a farm worker from Cornwall who had died in early December 1994, aged 54. There had been two confirmed cases of BSE on the farm, in August 1991 and October 1992. Additionally, a cow sold off the farm in December 1987 had been diagnosed with BSE in September 1988.224

5.34 On 1 December 1994, the case was reported in the local newspaper, The Cornishman, while the patient was still in hospital.225

5.35 On 19 December 1994, Mr Charles Lister, DH, minuted the private secretary to Baroness Cumberlege with information about this possible ‘third case in farmers/ farm workers who have had BSE cases in their herds’.226 This minute enclosed the article from The Cornishman and was copied to DH officials and to Mr Eddy at 219

YB94/1.14/1.2 220 YB94/1.26/3.1 221 YB94/1.26/2.3; YB94/1.14/1.2 222 YB94/1.26/2.2 223

The report formed Annex 2 to the CJDSU’s Third Annual Report (IBD2 tab 8) 224

YB94/12.19/3.1 225 YB94/12.19/3.4 226 YB94/12.19/5.1

EMERGENCE OF VARIANT CJD 39 MAFF. He noted that diagnosis would not be confirmed until post mortem, but the Surveillance Unit thought it highly likely to be CJD.

5.36 On the same day, Mr Thomas Eddy, MAFF secretary to SEAC, passed the newspaper article and basic information about the case on to MAFF Ministers and officials.227

5.37 On 13 January 1995, SEAC held a special meeting to discuss the significance of this third case of CJD in a farmer in the first four years of surveillance.228 Dr Sheila Gore, an epidemiologist from the MRC Biostatistic Unit, was invited as an independent expert.

5.38 Detailed consideration was given to the case itself and the epidemiological implications. Dr Will commented that the post-mortem results were not yet available, but it was highly likely that the diagnosis of CJD would be confirmed. He stated that the man had no significant medical history and that he had worked as a farm labourer on the same dairy farm since 1955: The man was known to have assisted with calving but never with any operative procedure; he rarely drank unpasteurised milk and never from BSE-affected animals. It was not known if he had ever eaten cattle feed.229

5.39 As to the epidemiological significance of the case, the members recalled the advice given by Professor Smith after SEAC had considered the second case of CJD in a farmer: Professor Smith had advised that if four cases arose in the first 5 years of the surveillance scheme the possibility of an association which was not due to chance had to be given very serious consideration.230

5.40 Dr Gore commented that: If the adult incidence of sporadic CJD in the UK was taken as one case per million (the figure used by Professor Smith) and if the same incidence applied to workers on dairy farms with BSE-affected herds, then the probability of observing three or more definite CJD cases in such workers in England and Wales in 5 years was low: 4 in 1,000. The probability was higher if the calculation was made using the total number of dairy farm workers in England and Wales. However, this was considered to be less relevant as the only reported cases of CJD in dairy farm workers since 1990 had been in lifetime dairy workers all with BSE-affected herds.


5.63 On 29 September 1995, various newspapers reported the third case of CJD in a dairy farmer.255 Reference was made to a letter published in The Lancet (dated 30 September 1995) by Dr (now Professor) Smith (LSHTM).

5.64 The letter reported: The occurrence of CJD in another dairy farmer with a potential occupational exposure to BSE is clearly a matter of concern. Statistical analysis indicates that the probability of discovering three or more dairy farmers with CJD by chance since 1990 in England and Wales ranges from 0.09 to 0.0002, depending on the occupational denominator (individuals who work on farms to full-time workers on BSE-affected dairy farms).256

5.65 Statistics for CJD in European farmers were also reported in the 30 September 1995 edition of The Lancet.257 The paper concluded that ‘there is no differential increase in the risk of CJD to farmers in the UK through potential occupational contact with cases of BSE’. On the continent there was also a slightly higher proportion of cases of CJD arising in farmers.258 This indicated that in the UK, CJD in farmers had probably not arisen from transmission of BSE.259

The fourth farmer – September 1995

5.66 On 28 September 1995, Dr Wright minuted the private secretary to the CMO about a probable fourth case of CJD in a farmer. The 59-year-old beef farmer lived in North Wales and was alive when the case was reported to the CMO. The farm, which had a 70-strong suckler herd, had a confirmed case of BSE about four years previously in a 4½ to 5-year-old cow.260

5.67 The minute recorded the urgency of dealing with the issue as the case was in the public domain and BBC Wales were making a programme referring to the case.261 An urgent meeting of SEAC was called for the following week.

5.68 On 4 October 1995, SEAC held a special meeting to discuss this further suspected case of CJD in a cattle farmer.262 Professor Smith (LSHTM) and Dr Cousens (LSHTM) were in attendance to provide the Committee with expert epidemiological advice.263 5.69 Dr Will advised that although the Unit had initially clarified the case as probable CJD, he felt that it was more appropriate to look at it as a suspect case. Consideration was given by SEAC to European data that showed 12 cases of BSE in France, along with a progressive neurological disease in a farmer associated with 255

YB95/9.29/12.1; YB95/9.29/10.1; YB95/9.29/14.1 256

Smith, P.E., Zeidler, M., Ironside, J.W., Estibeiro, P. and Moss, T.H. (1995) Creutzfeldt-Jakob Disease in a Dairy Farmer, The Lancet, 346, 898 257 Delasnerie-Laupretre, N., Poser, S., Pocchiari, M., Wientjens, D.P. and Will, R. (1995) Creutzfeldt-Jakob Disease in Europe, The Lancet, 346, 898 258 T71 p. 115 259 T24 p. 95 260 YB95/9.28/3.1 261 YB95/9.28/3.1 262 YB95/10.4/1.1–1.8 263 YB95/10.04/1.1

EMERGENCE OF VARIANT CJD 45 one of those cases. (In the eventuality, this farmer was not diagnosed with CJD. At the beginning of January 2000, there had been no reported cases of CJD in farmers in France where BSE had been found in that farmer’s herd.)

5.70 Mr Wilesmith gave SEAC information about the farm associated with the possible UK fourth case of CJD under discussion. The farm had not been visited by MAFF. It had one case of BSE in a purchased animal which died in September 1991. From available information, the animals had not been fed on concentrates (although this had not been double-checked). It was thought, however, that the farm did have a big poultry battery unit, which may have meant that ruminant-derived feed was available on the farm.

5.71 Dr Cousens made a presentation of the epidemiology.264 He had calculated age specific mortality rates for sporadic CJD from 1990 to 1994 and applied these to data on farmers to calculate the expected number of sporadic CJD cases in farmers. The following conclusions were reached: i. there had been an alarming number of cases in farmers who had had contact with cattle with BSE. However, other occupational groups, expected to carry greater risk (eg, abattoir workers, veterinary surgeons), did not appear to be affected; ii. it was now difficult to explain the cases as a chance phenomenon. Yet the absolute risk still remained extremely low; iii. it was unclear whether the possible risk factor might be associated with cattle with BSE or the food given to them; and iv. as there was a problem with establishing a causal link, transmission studies would be extremely important.

5.72 At this meeting, Dr Wight invited members of SEAC to make a fairly clear statement on how they viewed the significance of a fourth case and to consider whether they were satisfied that nothing else needed to be done in terms of practical measures.265 In evidence to the Inquiry, Dr Wight said that trying to get a clear statement as to what would be a significant number of cases in farmers was bound to be difficult. She said, ‘I do not think that SEAC any more than anybody else had any idea how to make sense of this at this stage.’266 At the meeting, Dr Tyrrell’s response was that although numbers were higher than expected, they were still extremely small. It would be irrational to take specific measures at the moment. Members of SEAC agreed to draw up a statement which the Department of Health could issue in response to media inquiries.267 The text of the statement included the following:268 The Committee concluded that it was difficult to explain this simply as a chance phenomenon. There is a statistical excess in cattle farmers compared with the general population but the absolute risk, even for farmers, is extremely low at about 2 cases per million per year. There may be other explanations for such an association besides infection with BSE, and the Committee noted that there are no recorded cases in other occupational 264

YB95/10.4/1.2–1.4 265 YB95/10.4/4.5 266 T71 pp. 135–6 267 YB95/10.4/4.5 268 YB95/10.4/4.9


46 groups such as veterinarians who might be expected to be similarly exposed. They also noted that the surveillance of CJD elsewhere in Europe has shown a similar incidence of CJD in farmers, including dairy farmers, in countries with no or very few cases of BSE. They therefore felt that it was important to undertake further epidemiological studies to detect any particular risk factors which might be involved, and reiterated their advice that the UK cases of CJD in cattle farmers and the strain of agent recovered from them should be studied in detail. The Committee have asked for further work to be done, but have not altered their advice to Government on the precautions necessary to protect either the public health, including farmers, and animal health.

5.73 Mr Eddy minuted the MAFF Minister and Parliamentary Secretaries advising them of the outcome of the SEAC meeting.269 He commented that SEAC had concluded that it would be worrying if the fourth case of CJD in a farmer from a BSE farm was confirmed. The chances of four CJD cases occurring randomly in farmers with BSE in their herds was . . . [since 1990] around 3/10,000. The Committee therefore concluded that it was difficult to explain the incidence as a chance phenomenon. This is a change to the Committee’s position; it had said that the most likely explanation of the three previous cases of CJD in dairy farm workers was that they were chance phenomena.270

5.74 Mr Eddy also stated that the SEAC did not recommend changes to any of the measures currently in place to protect human and animal health, including those of farmers and others handling cattle and BSE suspects.

5.75 On the same day, Mr Eddy prepared a second minute which was sent to Dr Matthews and Mr Keith Meldrum (CVO) amongst others about discussions during the SEAC meeting.271 Mr Eddy included a list of four ways in which the farmers might have been exposed to BSE that might have then led to their infection with CJD: i. cattle were excreting the agent in some form – no evidence for this; ii. meat and bone meal (MBM) in cattle feed – if so this would affect pig and poultry farmers equally (these feeds also contained MBM); iii. normal food – unclear why this discriminated in favour of farmers, although farmers could have been exposed to foods that other people might not have been routinely exposed to, such as unpasteurised milk; and iv. contact with animals – possibly animals killed on the farm.


5.93 Dr Will updated SEAC on CJD surveillance results at their 23rd meeting on 5 January 1996.292 He ‘reaffirmed that the incidence of CJD in dairy farmers in Europe showed an excess over the incidence for the population as a whole’. He confirmed that a 52-year-old abattoir worker from York was suspected of having CJD. The patient had worked mainly as a stockman in a mixed abattoir for 18 months in the late 1980s, and had occasionally pithed animals but had much less exposure than other abattoir workers. Dr Will believed that the patient was no more than a suspect at that stage.

5.94 The minutes of the meeting record that Professor Smith commented on this case: He [Professor Smith] felt that it was not possible to come to any conclusions on the basis of this case alone even if CJD is confirmed. Nevertheless, taking into consideration the affected farmers as well, and even though the abattoir worker was in an apparently relatively low risk category, the ‘box’ of ‘at 289 S61D Will para. 4 290 T138 p. 34 291 S61D Will para. 18 292

YB96/1.5/1.6–1.8; S61D Will paras 19–22

EMERGENCE OF VARIANT CJD 51 risk’ occupations was getting full compared to expectation on pure chance and could not be dismissed.293


Update on cases of CJD in farmers

5.152 During the period 1986–96, much attention and publicity was focussed on four cases of CJD in farmers (see above). Although those four cases were regarded as likely to be more than might be expected for the known population frequency of the disease, analysis of CJD in Europe showed the incidence of disease in farmers was similar to that in the UK.373 In addition, the clinical and pathological features of these cases were no different to those found in classical sporadic CJD.

5.153 It is understood that since 20 March 1996, at least two further cases of sporadic CJD in a relevant occupational group have been reported to the CJDSU, one in a farmer and another in an abattoir worker.374 Recent transmission studies in mice indicate that the causal agent in these cases has transmission characteristics (incubation period and neuropathology) which are distinct from both vCJD and BSE, and that the protein deposited in the brain in all of these cases has a glycosylation pattern distinct from the type 4 pattern observed in vCJD and BSE.


Is occupation a risk factor in vCJD?

5.192 One of the original proposals in the CJD surveillance project was to monitor occupational groups exposed to BSE-affected cattle and their products. Such groups include farmers, veterinarians, slaughtermen and butchers. This part of the project was given a low priority by the Tyrrell Committee and was not implemented. It was felt that rather than set up longitudinal study of a fixed number of individuals in each group, together with matched controls, it would be adequate to take an occupational history of each CJD case at the time of referral.

5.193 From 1990 to 1996, the CJDSU had referred to it four farmers affected with CJD who were known to have had cases of BSE on their farms. Assuming a total of 155,000 dairy farmers in the UK,384 the number of observed CJD cases is significantly higher than expected from population estimates. Counting only those farmers with affected cattle, the probability of observing four or more confirmed cases of CJD is estimated at less than one in 10,000.385 In addition, two farmers’ wives were known to have CJD from farms in which clinical BSE had not been reported (although preclinical cases of BSE on these farms might have been expected). 384 Gore, S. (1995) More than Happenstance: Creutzfeldt-Jakob Disease in Farmers and Young Adults, British Medical Journal, 311, 1416–8 385 Ibid.


5.194 The affected farmers were aged between 54 and 64 and had signs and symptoms typical of sporadic CJD. Two had EEG changes typical of the sporadic disease and all four had type 2 glycosylation patterns. Three farmers were homozygous for methionine at codon 129 and the fourth was a valine homozygote. None conformed to the phenotype characteristic of vCJD. The findings remained unexplained, although a European collaborative study showed a similar increased incidence in deaths due to CJD in farmers in several member states. It was noted that unexpected numbers of affected individuals occurred in other occupational groups, such as the clergy, but numbers in each occupation remained small.

5.195 Among occupational groups exposed to BSE, farmers remain unusual in having such an excess over the incidence of CJD for the population as a whole. No cases of CJD have been reported amount veterinarians exposed to BSE. Four people in the meat industry (butchers, abattoirs, rendering plants, etc) have been reported to have vCJD.386 The present evidence has been accepted by some as reassuring in that such occupations may not pose as serious a risk as might have been expected.

This was not simply another farmer but the third farmer......

suspect case of CJD in a farmer who has had a case of BSE in his beef suckler herd.

cover-up of 4th farm worker ???


now story changes from;

SEAC concluded that, if the fourth case were confirmed, it would be worrying, especially as all four farmers with CJD would have had BSE cases on their farms.


This is not unexpected...

was another farmer expected?

4th farmer, and 1st teenager

2. snip...

Over a 5 year period, which is the time period on which the advice from Professor Smith and Dr. Gore was based, and assuming a population of 120,000 dairy farm workers, and an annual incidence of 1 per million cases of CJD in the general population, a DAIRY FARM WORKER IS 5 TIMES MORE LIKELY THAN an individual in the general population to develop CJD. Using the actual current annual incidence of CJD in the UK of 0.7 per million, this figure becomes 7.5 TIMES.

3. You will recall that the advice provided by Professor Smith in 1993 and by Dr. Gore this month used the sub-population of dairy farm workers who had had a case of BSE on their farms - 63,000, which is approximately half the number of dairy farm workers - as a denominator. If the above sums are repeated using this denominator population, taking an annual incidence in the general population of 1 per million the observed rate in this sub-population is 10 TIMES, and taking an annual incidence of 0.7 per million, IT IS 15 TIMES (THE ''WORST CASE'' SCENARIO) than that in the general population...


20 year old died from sCJD in USA in 1980 and a 16 year old in 1981. A 19 year old died from sCJD in France in 1985. There is no evidence of an iatrogenic cause for those cases....

snip... see full text ;

Monday, May 19, 2008


-------- Original Message --------

Subject: Occupational risk factors for the sporadic form of Creutzfeldt-Jakob disease (FULL TEXT)

Date: Sat, 29 Nov 2003 13:09:20 –0600

From: "Terry S. Singeltary Sr."

{please note, scanned, copied, and corrected, could be errors..TSS)

La Medicina del Lavoro Med Lav 2003; 94,4:353-363

Occupational risk factors for the sporadic form of Creutzfeldt-Jakob disease


Dipardmento di Sanita Pubblica, Sezione di Medicina del Lavoro, Universita di Cagliari * Isdtuto di Medicina del Lavoro, Facolta di Medicina e Chirurgia A. Gemelli, Universita Cattolica del Sacro Cuore, Roma


Creutzfeldt-Jakob disease; epidemiology; occupational health


Some case reports among European farmers and a few case-control studies suggested the hypothesis of an increased risk of the sporadic form of CJD (sCJD) associated with livestock farming or work as a butcher. Also, the discovery of the possibility of transmission of the disease via blood or by contact following corneal or dura madre transplant suggested that health occupations might also run higher sCJD risks. However, a meta-analysis of three case-control studies and a multicentre European study did not find any positive association between sCJD and health-related jobs or occupational contact with livestock, such as cattle and sheep, or animal products. To explore possible occupational risk factors for Creutzfeldt-Jakob disease (CJD), we used a publicly available US database including about 6 million deaths in 24 states during 1984-95. Cases were 636 deaths (300 men and 336 women) with CJD (ICD-9 code 046.1) as the underlying cause of death. Controls were 3,180 deaths randomly selected from among those who died from all other diseases except those affecting the central nervous system. CJD cases represented a wide variety of occupations (159) and industries (147). Among occupations and industries, for which previous reports suggested potential exposure to a transmissible spongiform encephalopathy (TSE) agent, the OR for CJD was significantly increased among butchers (OR=6.8, 95% C.I. 1.5, 30.1, based on 4 cases and 3 controls), and persons working in offices of physicians (OR=4.6, 95% C.I. 1.2, 17.6 based on 5 cases and 4 controls). Nine other occupations and seven other industries, for which no previous suggestion existed in the literature, also showed significant associations. Overall, our results suggest that occupational exposures are not an important source of sCJD infection. However, as the excess among butchers and some workers in health occupations was consistent with previous reports, more indepth research is warranted to address the hypothesis.


«Fattori di rischio professlonale per la forma sporadica della malattia di CreutzfeIdt-Jakob». L'epidemia delta cosiddetta "nuova variante" della malattia di Creutzfeldt-Jakob (CJD) in Gran Bretagna, e la sua dimostrata associazione con l'epidemia di encefalopatia spongiforme bovina (BSE) in quello stesso Paese, hanno ridestato l'in-

Pervenuto il 28.11.2002 - Accettato il 15.1.2003

Corrispondenza: Diparrimento di Sanita Pubblica, Sezione di Medicina del Lavoro, Universita di Cagliari, via San Giorgio 12,

09124 Cagliari - Tel. 070-60285278 - Fax 070654350 - E-mail:

Comunicazione orale alia XXV Riunione Annuale dell'Associazlone Italiana di Epidemioloeia, Venezia 4 Ottobre 2001



teresse nei confronti di tutte leforme di questa rara malattia e del suo possibile rapporto con alcune esposizioni in amblto lavorativo. La descrizione di alcuni casi di CJD in contadini europeifece ipotizzare che attivita quail l'all-evamento di bovini o l'abbattimento degli stessi in mattatoi potessero comportare un aumento del rischio di CJD. Inoltre, la possibility di una trasmissione per via ematica o per contatto con materiali biologici, successivamente ai trapianfi di dtira madre o di cornea, fece sospettare che anche le professioni sanitane potessero comportare un aumento del rischio di CJD. Tuttavia, una meta-analisi di tre studi caso-controllo non dimostro una associazione tra forma sporadica di CJD ed attivita sanitarie o contatto con bovini ed ovini, ed uno studio multicentrico Europeo non trovb akuna associazione con I'esposizione professionale ad animali o pelli, mentre itrischio risultava elevato perfrequents esposizlone a cuoio ed esposizione a fertilizzanti contenenti zoccoli e coma. La dispombilita di un data-base pubblicamente accessible, contenente i dati di circa 6 milioni di certificati di morte in 24 Stati degli Stati Uniti nel periodo 1984-95, ha consentito I'esplorazione dei rischi occupazionali di CJD in questo Paese. Sono stati individual in tutto 636 casi (300 uomini e 336 donne) di decessi per CJD (ICD-9 046.1). Come controlli sono stati selezionati 3180 soggetti deceduti per altre patologie, ad esclusione di quelle a carico del sistema nervoso centrale, accoppiati in rapporto di 5:1 ai casi per area geografica'di residenza, sesso, razza edeta. Tra le occupaziom sospettate a priori di un'associazione, i macellai mostravano un OR di 6,8 (I.F. 95% 1,5, 30,1, basato su 4 casi e 3 controlli), ma un risultato simile veniva osservato anche in altre nove occupazioni non sospettate a priori di un'associazione. Il rischio non risultava elevato per Ie attivita agricole nel complesso, o nelle Industrie alimentan, mentre un OR di 4,6 (I.F. 95% 1,2, 17,6, basato su 5 casi e 4 controlli) era associate al lavoro in ambulaton medici, ma non in ospedali o altri servizi sanitari. Altre sette attivita industriali, non sospettate a priori di un'associazione, mostravano un significative aumento del rischio di CJD. La dispersione dei casi di CJD in una grande varieta di occupazioni induce a ritenere che le esposizioni professionali contribuiscano scarsamente all'eziologia della forma sporadica di CJD. D'altro canto, i risultati positivi potrebbero essere genera ti dal caso data la molteplicita di con-fronti effettuati. Tuttavia, appare opportuna la pianificazione di indagini multicentriche piu approfondite che testino l'ipotesi del ruolo di esposizioni professionali nell 'attivita di abbattimento degli animali, insieme ad altri possibili fattori di rischio, nell'eziologia di questa rara malattia.


The UK epidemics of the new variant form of Creutzfeldt-Jakob disease (nvCJD), and its link with bovine spongiform encephalopathy (BSE) (46, 47) has raised interest in searching for etiolog- ical clues for the more commonly seen, classic forms of CJD. Classic CJD is a neurological disor- der, classified in the group of transmissible spongi- form encephalopathies (TSEs), that has been esti- mated to affect approximately 1x10-6 persons per year worldwide. It is invariably fatal, with a mean illness duration of 5 months (47), and a median age at death of 68 years (20). Some TSEs in humans have been shown to be associated with mutations in the prion protein (PrP) gene (PRNP) on chro- mosome 20 (32), and a few are classified as familial CJD. In patients affected by the non-familial spo- radic form of classic CJD (about 85% of CJD cas- es), a significantly increased prevalence of homozy-gosity for methionine or valine at PrP codon 129 has been reported (25, 28, 37, 40). Based on the scarce geographical variation in the occurrence of sporadic CJD over long time periods, it has been proposed that there is no environmental source of infection (16, 31) and that the vast majority of cas- es rather result from de novo spontaneous genera- tion of a transmissible agent consisting of an ab- normal form of a host-encoded glycoprotein (31). This transmissible agent was given the name of "prion" in 1982 (30). However, a 5-fold inter-re- gional variation in the crude CJD mortality rate occurred within Italy in 1993-99 (8). Also, the pro- portion of polymorphism at codon 129 among sCJD cases is more similar to that observed among persons with iatrogemc CJD, than to that in the general population, which suggested that simple stochastic events would not fully explain SCJD (33). Also, sCJD cases are tipically elderly, with cortical symptoms, and abnormal PrP, but not amyloid, deposits in the synapses, On the other hand, nvCJD typically affects young people; it is not associated with codon 129 polymorphism and it does present amyloid plaques in the brain (47).



A substantial body of evidence supports the hy- pothesis of blood transmission of the sCJD agent in various animal species (41), depending on the tissue level of PrP infectivity, the species barrier, and the route of administration (33). However, the risk of CJD transmission by transfusion remains theoretical, since no confirmed cases have ever been causally attributed to the receipt of a blood transfusion, nor has any case developed in recipi- ents of clotting factor concentrates, or pooled plas- ma derivatives, to which a donor, who subsequently developed CJD, had contributed (15, 27, 41). Also, no known cases of CJD were attributable to the reuse of percutaneous transluminal coronary angio- plasty (PTCA) equipment contaminated by blood (15). While the potential exists for blood transmis- sion of the disease, thus far human epidemiological evidence suggests that such an occurrence would be rare, as only a small fraction of the general popula- tion carrying codon 129 and codon 200 polymor- phisms might be susceptible to infection, and most transfusions might not contain infective doses suf- ficient to cause the disease (33). On the other hand, the hypothesis of a transmissible agent, pos- sibly with blood, is supported by numerous clinical reports of iatrogenic CJD consistently identifying surgical procedures as a risk factor. Although such a possibility was ruled out in an early study among French cases occurring in 1968-77 (4), CJD cases have been described after dura madre or corneal transplants from infected donors (14, 21, 24, 26, 27, 29), neurosurgery of stereotactical encephalog- raphy with contaminated instruments (3, 49), use of GH hormonal extracts from cadavers (2), and three epidemiological studies showed a higher sCJD risk following general surgery (9, 22, 43). However, while Australian authors interpreted the evidence as an indication of the possibility of dis- ease transmission (9), German authors suggested stress as the relevant risk factor (22). Due to the exceptional resistance of the infecting agent to common sterilising agents, autoclave and sodium hypochloride or hydroxide treatment, or formic acid treatment of infected materials and instru- ments has been suggested to prevent occupational and/or iatrogenic transmission of the disease (34, 36), while formadehyde was not effective in pre- venting transmission (33).

If blood transmission were important, occupa- tional contact with animal blood, organs, and other animal products would be a plausible co-factor in sCJD etiology. In the pre-nvCJD-epidemic era, the hypothesis of CJD as a zoonotic disease was raised (23). As early as 1986, such a hypothesis was again raised in a small French study (11). Occupational contact with animals such as deer, monkeys, and squirrels was associated with a non-significant 9- fold increase in risk, while the excess risk of similar degree associated with non occupational contact with deer or rabbits was statistically significant. Exposure to animal organs was also significantly associated with CJD (OR=20.9; p<0.005) (11). Following the nvCJD epidemics in the UK, clinical reports of sCJD cases among livestock farmers and butchers have been repeatedly published (17, 35, 44, 48), further suggesting that - if the link were to be confirmed in analytical studies — transmission via the blood or skin contact through skin lesions with infected materials and/or instruments would be important (19). Analytical studies have been less numerous, and they are reported in table 1. A meta-analysis of three case-control studies on sCJD published at that time concluded that a non significant association existed with livestock farm- ing and with health related occupations (45). The study of 662 sCJD deaths in 1970-96 in the Unit- ed Kingdom found a significant excess risk among livestock farmers (6 observed deaths versus 2.4 ex- pected), although the interpretation was limited to the absence of any link with the nvCJD epidemics (10). All the observed cases were livestock farmers, four of whom (0.6 expected) occurred in farms where BSE cases had been reported. No cases were observed among veterinarians (0.03 expected), or butchers. (0.15 expected). A matched case-control study of 206 sCJD cases and controls did not iden- tify any association with a priori suspected occupa- tions (38). However, 21 cases (10%) e 14 controls (7%) occurred in subjects with occupational contact with animal products (p=0.17). The authors did not explore this finding in detail. We conducted a crude calculation based on the published data, and we found instead an Odds Ratio of 1.6 (95% confi- dence interval 1.18,2.15).



Table 1 - Studies of sCJD and occupation


Type of study Health Raising Butchers,

occupations cattle/sheep abattoir workers

Wientjens et al, 1996

Cousens et al, 1997

UK Nat CJD Surv Unit, 1997

Van Duijn et al, 1998

Aylin et al, 1999

UK Nat CJD Surv Unit, 2001**

Meta-analysis Cohort



Trend in proportional mortality


snip...not available...tss

* contact with animal products; ** combining nvCJD and sCJD cases

A European case-control study was conducted by interviewing next-of-kins of 405 CJD cases and 405 hospital controls, excluding patients suffering from dementia (42) .The authors reported a signifi- cant excess risk associated with the use of fertilizers containing substances derived from hoofs and horns, and with contact with skin and fur not as garments. Among individual occupations, only butchers showed a non-significant increase in the Odds Ratio. A proportional mortality analysis of deaths from dementia in England and Wales dur- ing 1979-96 did not find a consistently increasing temporal trend in occupations suspected a priori of being at risk, such as farmers, butchers and abattoir workers, and veterinarians (1). Another prelimi- nary combined case-control analysis of 102 nvCJD cases and 197 sCJD cases, compared to 195 con- trols, found no excess risk among health related oc- cupations, butchers and abattoir workers, and other occupations involving contact with animal products (39). Eight out of 114 identified cases in Slovakia had health related occupations (25).The authors excluded a link between occupational factors and CJD risk, although no formal analysis was con- ducted in this regard, nor any information was pro- vided on which were the occupations of the other 106 cases.

It is possible that, in the studies conducted thus far, the small number of subjects in the occupations at risk limited the exposure assessment to ever hav- ing held a job considered a priori at risk, indepen- dently of the period in the lifetime, duration, type of animals, and actual job content. The methods section of these papers do not explain whether complete work histories were included in the ques- tionnaire, or whether only one or more main occu- pational titles or the last were collected. A further problem in these studies is that information for cases always relied on next-of-kin reporting, whilst the same study subjects provided the information in about half the hospital controls and in all popu- lation controls.

Overall, the results of the studies conducted thus far stress the fundamental requirement of having experts in occupational epidemiology, agricultural work technology and veterinarian hygiene par- ticipating in planning and analyzing occupational data.

To examine the possible association of CJD with occupational risk factors, we accessed a large pub- licly available database, including death certificate from 24 US states in 1984-95, to analyze the occu- pations of the 636 deaths due to CJD therein re- ported in comparison to 3,180 controls deceased from other selected causes of death, in a country thus far not affected by the nvCJD epidemics.


The 24 US states death certificates database we used consists of several million coded death certfi- cates from 24 US states, covering the years 1984- 95. The 24 states are: Colorado, Georgia, Idaho (from 1988), Indiana (from 1986), Kansas, Ken- tucky, Missouri (in 1984-86), Maine, Nebraska (in



1984-85), Nevada, New Hampshire, New Jersey (from 1988), New Mexico (from 1986), North Carolina (from 1987), Ohio (from 1985), Okla- homa, Rhode Island, South Carolina, Tennessee (in 1985-88), Utah (from 1985), Vermont, West Virginia (from 1988), Washington (from 1989), and Wisconsin. In addition to standardized coding procedures, information on usual occupation and kind of business or industry, reported in the death certificate for each decedent, was included in the database provided to the National Center for Health Statistics (NCHS) (7). The information on occupation and industry was coded according to the 1980 US Bureau of the Census classification (6). The underlying cause of death was coded ac- cording to the International Classification of Dis- eases - 9th revision. No further details, such as du- ration of employment or concurrent diseases, are available from this database. Among subjects 25 years of age or more at death, 636 cases of CJD (ICD-9 code 046.1) were identified. Table 2 shows the case distribution by age, and gender. Only 22 subjects were indicated as non-whites in the data base. As we did not see any reason why a gross def- inition of genetic background, such as the demo- graphic concept of "race", should affect sCJD risk, we included all subjects in the analysis. Eligible controls were subjects who died from all other dis- eases, except mental disorders (ICD-9 codes 290.0-319.9), diseases of the central nervous sys- tem (ICD-9 codes 320.0-349.9), cerebrovascular diseases (ICD-9 codes 430.0-438.9), unspecified atherosclerosis (ICD-9 code 440.9), and ill defined conditions and symptoms involving the central nervous system (ICD-9 codes 780.0-781.9). We randomly selected five controls per each case with- in the set of controls with the same geographic re- gion, race, gender, 5-year age group, and year of death as the index case. The Odds Ratio (OR) as- sociated with a given occupation or industry cate- gory was expressed relative to an unexposed refer- ence group including all other occupation or indus- try categories.

Table 2 - Deaths from Creutzfeldt-Jakob disease in 24 US states in 1984-95 by age, and gender

Age group Men Women

25-39 3 4

40-49 11 16

50-59 47 46

60-69 126 121

70-79 92 117

80 + 21 32

All ages 300 336

Odds Ratios (ORs) and their 95% confidence intervals (95% C.I.) were derived from the respec- tive log odds obtained with logistic regression modeling, using the GMBO feature of the Epi- cure® software. ORs were calculated for selected demographic variables. We first calculated OR for those occupations and industries for which litera- ture reports suggested a potential association with CJD. For occupations, these prior hypotheses were livestock farmers, veterinarians, butchers and other food-related occupations, pathologists and other health professionals. For industries, those consid- ered as prior hypotheses were livestock tanning, slaughterhouses and meat processing plants, hospi- tals and other health facilities. Secondly, we calcu- lated OR for all occupations and industries for which there were three or more exposed cases. Co- variates in the logistic regression model for occupa- tion and industry were age (5-year age categories), marital status (never-married versus ever-married), and socioeconomic status (SES) (five categories). The SES indicator was obtained by categorizing the Greens Standardized Scores for Specific Occu- pations (13,18), as follows:

- low SES (score 21-39);

- medium-low SES (score 40-49);

- medium SES (score 50-59); 4. medium-high SES (score 60-64);

- high SES (score >65). Introducing gender as a covariate in the logistic regression model did not change the risk estimates.


In the present study population, female cases are more numerous than male, and more than 94 per- cent of the cases died at age 50 or older (table 2). Subjects who died from CJD were less likely to have never been married and to have lived in the South, and slightly more likely to have resided in metropol- itan areas (not shown in the tables). The OR for CJD increased with higher SES (test for trend, p<0.001). This association persisted within strata of latitude, geographic region, race (although numbers were very small among African Americans), gender, age, and marital status (not shown in the tables).


Overall, 159 occupation and 147 industry cate- gories were represented among CJD cases, with 52 of the occupation and 54 of the industry categories composed of at least three cases. A statistically sig- nificant association with CJD was observed for 10/52 occupation categories (19%) and 8/54 indus- try categories (15%), including disparate activities such as financial managers, mechanical engineers, teachers, military personnel, and persons working in manufacture of toys, amusement, and sporting goods, telephone utility companies, beauty shops, and financial services (table 3). These associations varied very little after limiting the analysis to sub- jects aged 40 years or older.

Among food handling occupations, a prior hy- pothesis in this study, a statistically significant asso- ciation was observed for butchers (OR=6.8, 95% C.I. 1.5, 30.1, based on 4 cases and 3 controls). The OR was non-significantly elevated for miscella- neous food preparation occupations (Census code 444: OR=3.2, 95% C.I. 0.9, 10.7, based on 4 cases and 9 controls), a heterogeneous category which in- corporates food preparation occupations other than those with specific codes (such as cooks, waiters, or bartenders). When we combined all food prepara- tion occupations, no association was observed (OR=1.1; 95% C.I. 0.5,2.3, based on 9 cases and 41 controls), suggesting that the observed excesses were restricted to butchers and miscellaneous food preparation occupations. No cases or controls were coded as non-farm animal caretakers. One case and no controls were classified as a hunter or trapper. When examined by industry grouping (table 3) the ORs were non significantly elevated in the meat products industry (OR=3.8, 95% C.I. 0.8, 17.3, based on 3 cases and 4 controls).

CJD was not associated with agricultural work. The occupation of non horticultural farmer showed a non significant 20% increase in risk. Among in- dustries, a similar result was observed for crop pro- duction (OR=1.2; 95% C.I. 0.6, 2.4, based on 12 cases and 73 controls), and livestock farming (OR=1.2, 95% C.I. 0.3, 4.2, based on 3 cases and 17 controls).

Health-related occupations and industries were also a prior hypothesis in this study. The excess ob- served among physicians was not statistically sig- nificant (OR=4.6, 95% C.I. 0.7, 29.0, based on 3 cases and 2 controls). No excess was observed for nurses (occupational codes 095 and 207 combined:

OR=0.8, 95% C.I. 0.4, 1.5; based on 12 cases and 55 controls), or for all health related occupations combined (OR=0.8; 95% C.I. 0.5, 1.5, based on 13 cases and 72 controls). No pathologists were re- ported among cases. No veterinarians were report- ed among cases versus one among controls.

Among health-related industries, a significant association was observed for persons working in offices of physicians (OR=4.6, 95% C.I. 1.2, 17.6, based on 5 cases and 4 controls), but not for those working in hospitals (OR=1.0, 95% C.I. 0.6, 1.7, based on 22 cases and 95 controls), or health ser- vices not elsewhere classified (OR=1.1, 95% C.I. 0.3, 3.8, based on 3 cases and 13 controls).

For the occupations and industries shown in table 3, being a prior hypothesis of this study did not increase the likelihood of a significant association with CJD (1/6 or 17% significant findings among prior hypotheses versus 9/46 or 20% among the other occupations, and 1/7 or 14% among prior hypotheses compared with 7/47 or 15% among the other in- dustries).


In this death certificate based case-control study, we observed a statistically significant association of CJD with work as a butcher and with employment in the office of a physician, occupation and indus- try categories for which previous literature reports suggested potential exposure to a TSE agent. However, other occupations and industries for which the same hypothesis was raised, such as work on a livestock farm, were unassociated with CJD. The positive associations with the occupation of butcher and employment in physician's offices cannot be conclusively interpreted because of the small numbers and lack of information on the type and extent of exposure to potentially infectious material. Also, other generally smaller studies of CJD in Europe have not found specific associa- tions with livestock farming or other specific occu- pations, including health care workers (1,42).


In our study, significant associations were found for CJD with 19 percent of the occupations and 15 percent of the industries composed of at least three cases, and these proportions did not vary according to being a prior hypothesis in this study or not. A proportion of positive findings (about 5%) would be expected to occur by chance. Relative differences in ascertainment may also have contributed to pos- itive findings for some high SES employment cate- gories, such as financial managers, engineers, teachers, drafting occupations, or work in insurance firms and financial industries. In this data set, risk for other neurological diseases, including amyothrophic lateral sclerosis, multiple sclerosis, and Parkinson's disease, also showed this pattern (data not shown), suggesting a generalized diag- nostic bias related to SES in diseases requiring a more sophisticated diagnostic evaluation. The pos- sible under-ascertainment of CJD deaths in the lower SES categories may also explain some of the deficit in CJD mortality previously reported among African Americans compared to whites in the USA (20). Therefore, as described in the methods sec- tion, we adjusted by SES all risk estimates. The in- crease in CJD risk for butchers and employees in physicians offices persisted in the unadjusted analysis or when the analysis was restricted to the SES category they belonged.

An important limitation in our study is that it was based on the one occupation and industry combination on the death certificate of study sub- jects, and no further details, such as duration of employment, were available. This should be con- sidered when interpreting our findings. One strength of our study is the large number of CJD deaths available for analysis (636 cases), as we uti- lized the largest database possible to evaluate the relationship of CJD with occupational risk factors. Still, the numbers for specific occupations and in- dustries are quite small, and chance could account for the increases in risk observed in our study.

Disease misclassification was likely to be a mi- nor problem in this study, as death certificates have been shown to be a reasonably specific source for ascertaining CJD cases (5, 12), and control subject;

were selected after excluding deaths linked to diag- nostic codes conceivably including misdiagnosed CJD cases. However, as it is not possible to distin- guish familial from non-familial CJD cases within a data base of coded death certificates, we cannot assess whether and to what extent individual find- ings may have been biased by poor diagnostic in- formation.

While chance could account for the associations we observed, their consistency with other pub- lished clinical and epidemiological reports indicate that further in-depth studies are warranted to eval- uate the findings among butchers and employees in physician's offices before concluding for a CJD ex- cess in these jobs. The rarity of the sCJD has pre- vented substantial progress in the knowledge of its etiological factors. The international multicentre approach, and a detailed occupational exposure as- sessment performed by experts, would be crucial in successfully identifying candidate risk factors...


Table 3 - Odds Ratio for Creutzfeldt-Jakob disease associated with selected industries and occupations (at least 3 exposed cases)


007 - Financial managers 6/5 4.2 (1.2-14.8)

019 - Managers and administrators, n.e.c. 36/151 0.9 (0.5-1.3)

023 - Accountants and auditors 6/24 0.9 (0.4-2.4)

056 - Industrial engineers 3/3 3.0 (0.6-15.6)

057 - Mechanical engineers 7/4 6.0(1.6-22.2)

084 - Physicians 3/2 4.6 (0.7-29.0)

095 + 207 - Registered nurses & licensed practical nurses 12/55 0.8 (0.4-1.5)

156 - Teachers, elementary school 16/63 1.0(0.5-1.8)

157 - Teachers, secondary schools 3/4 2.8 (0.6-12.8)

159 - Teachers, n.e.c. 5/6 3.5 (1.0-11.8)

176 - Clergy 3/14 1.1 (0.3-3.9)

185 - Designers 3/8 1.4 (0.4-5.5)

217 - Drafting occupations 3/4 3.8 (0.8-17.2)

243 - Supervisors and proprietors, sales occupations 22/97 1.1 (0.7-1.8)

253 - Insurance sales occupations 5/11 1.8 (0.8-5.3)

254 - Real estate occupations 3/9 1.3 (0.3-4.8)

259 - Sales representatives, mining, manufacturing, wholesale 7/16 1.7 (0.7-4.2)

263 - Sales workers, motor vehicles and boats 4/9 2.2 (0.7-7.0)

274 - Sales workers, other commodities 8/59 0.7 (0.3-1.4)

313 - Secretaries 14/73 1.0 (0.5-1.7)

337 - Bookkeepers, accounting, and auditing clerks 8/30 1.3 (0.6-2.9)

379 - General office clerks 10/30 1.7 (0.8-3.4)

407 - Private household cleaners and servants 9/39 1.7 (0.8-3.8)

417 - Firefighting occupations 3/7 2.1 (0.5-8.1)

435 - Walters and waitresses 4/22 1.1 (0.4-3.4)

436 - Cooks, except short order 5/30 1.1 (0.4-2.8)

444 - Miscellaneous food preparation occupations 4/9 3.2 (0.9-10.7)

447 - Nursing aides, orderlies, and attendants 3/39 0.5 (0.1-1.6)

449 - Maids and housemen 3/7 2.8 (0.7-11.0)

453 - Janitors and cleaners 5/50 0.7(0.3-1.7)

458 - Hairdressers and cosmetologists 6/8 3.7 (1.3-10.7)

473 - Farmers, except horticultural 14/87 1.2 (0.6-2.3)

518 - Industrial machinery repairers 3/3 5.2 (1.0-26.1)

529 - Telephone installers and repairers 3/2 7.2 (1.2-43.4)

558 - Supervisors, n.e.c. 3/17 0.9 (0.2-2.9)

563 - Bnckmasons and stonemasons 3/4 5.0(1.1-22.7)

567 - Carpenters 4/41 0.6 (0.2-1.7)

575 - Electricians 4/15 1.3 (0.4-4.0)

633 - Supervisors, production occupations 10/40 1.2 (0.6-2.5)

637 - Machinists 6/22 1.3 (0.5-3.3)

653 - Sheet metal workers 3/4 3.8 (0.8-17.2)

686 - Butchers 4/3 6.8 (1.5-30.1)

744 - Textile sewing machine operators 5/28 1.2 (0.4-3.1)

757 - Separating, filtering &, clarifying machine operators 3/2 7.2 (1.2-43.4)

779 - Machine operators, not specified 10/25 2.0 (0.9-4.2)

783 - Welders and cutters 3/20 0.9 (0.3-3.2)

785 - Assemblers 9/31 1.9 (0.9-4.2)

804 - Truck drivers, heavy 7/62 0.7(0.3-1.5)

844 - Operating engineers 3/7 2.1 (0.5-8.1)

877 - Stock handlers and baggers 3/8 2.0 (0.5-7.6)

889 - Laborers except construction 16/93 1.3 (0.7-2.5)

905 - Military 10/23 2.2 (1.0-4.6)

Table 3 - continued

Census/Code Cases/Controls OR (95% C.I.)


010 - Agricultural production, crops 12/73 1.2 (0.6-2.4)

O11 - Agricultural production, livestock 3/17 1.2 (0.3-4.2)

060 - Construction 26/179 0.8 (0.5-1.2)

100 - Meat products 3/4 3.8 (0.8-17.3)

142 - Yarn, thread and fabric mills 10/49 1.2 (0.6-2.4)

151 - Apparel and accessories, except knit 3/23 0.8 (0.2-2.6)

160 - Pulp, paper, and paperboard mills 4/12 1.7 (0.5-5.3)

172 - Printing and publishing, except newspapers 4/20 0.9 (0.3-2.8)

181 - Drugs manufacturing 3/5 3.0 (0.7-12.7)

192 - Industrial and miscellaneous chemicals 3/14 1.1 (0.3-3.9)

200 - Petroleum refining 3/11 1.2 (0.3-4.6)

270 - Blast furnaces, steelworks, rolling, and finishing 9/27 1.7 (0.8-3.7)

280 - Other primary metal industries 3/6 2.6 (0.6-10.3)

320 - Metal working machinery manufacturing 3/4 3.6 (0.8-16.4)

331 - Machinery except electrical, n.e.c. 5/20 1.1 (0.4-3.0)

342 - Electrical machinery, equipment and supplies 4/24 0.8 (0.3-2.4)

351 - Motor vehicles and motor vehicle equipment 13/43 1.7(0.9-3.1)

352 - Aircrafts and parts 6/16 1.8 (0.7-4.5)

371 - Scientific and controlling instruments 3/7 1.9 (0.5-7.5)

390 - Toys amusement, and sporting goods 3/1 18.3 (1.9-177)

392 - Not specified manufacturing industries 11/57 1.1 (0.6-2.1)

400 - Railroads 4/31 0.6 (0.2-1.8)

410 - Trucking service 9/51 1.0 (0.5-2.0)

441 - Telephone (wire and radio) 10/17 2.7 (1.2-5.9)

552 - Wholesale trade of petroleum products 3/4 3.8 (0.8-17.1)

601 - Grocery stores 4/33 0.6 (0.2-1.8)

612 - Motor vehicle dealers 9/25 1.8 (0.8-3.9)

620 - Auto and home supply stores 3/5 2.9 (0.7-12.1)

621 - Gasoline service stations 6/12 2.8 (1.0-7.4)

630 - Apparel and accessories stores, except shoe 4/17 1.1 (0.4-3.3)

641 - Eating and drinking places 13/70 1.0(0.5-1.8)

682 - Miscellaneous retail stores 3/13 1.1 (0.3-3.9)

691 - Not specified retail trade 3/25 0.6 (0.2-1.9)

700 - Banking 6/14 1.7 (0.7-4.6)

710 - Security, commodity brokerage, & invest, companies 3/4 3.5 (0.8-15.8)

711 - Insurance 17/29 2.6 (1.4-4.7)

712 - Real estate 9/30 1.3 (0.6-2.7)

742 - Business services, n.e.c. 3/18 0.8 (0.2-2.6)

751 - Automotive repair shops 4/18 1.3 (0.4-3.9)

760 - Miscellaneous repair services 3/15 1.1 (0.3-3.7)

761 - Private households 9/46 1.4 (0.7-3.1)

772 - Beauty shops 6/10 3.0(1.1-8.3)

812 - Offices of physicians 5/4 4.6 (1.2-17.6)

831 - Hospitals 22/95 1.0(0.6-1.7)

832 - Nursing and personal care facilities 3/21 0.8 (0.2-2.6)

840 - Health services, n.e.c. 3/13 1.1 (0.3-3.8)

842 - Elementary and secondary schools 34/128 1.2(0.8-1,8)

880 - Religious organizations 3/23 0.7 (0.2-2.3)

890 - Accounting, auditing, and bookkeeping services 4/9 1.9 (0.6-6.1)

901 - General government, not elsewhere classified 6/37 0.8 (0.3-1.8)

910 - Justice, public order, and safety 8/34 1.1 (0.5-2.5)

921 - Public finance, taxation, and monetary policy 4/3 5.5 (1.2-24.8)

931 - Administration and economic programs 3/10 1.4(0.4-5.0)

942 - Armed Forces 10/22 2.3 (1.1-4.9)

Note: N.e.c. = not elsewhere classified


1.AYLIN P, BUNTING J, DE STAVOLA B, COLEMAN MP: Mortality from dementia in occupations at risk of exposure to bovine spongiform encephalopathy: analysis of death registrations. Br Med J 1999; 318: 1044-1045

2. BILLETTE DE VILLEMEUR T, DESLYS JP, PRADEL A, et al: Creutzfeldt-Jakob disease from contaminated growth hormone extracts in France. Neurology 1996; 47: 690- 695

3. BROWN P: Environmental causes of human spongiform encephalopathy. In Baker H, Ridley RM (eds): Methods in Molecular Medicine: firion diseases. Totawa (NJ): Hu- mana Press Inc, 1996:139-154

4. BROWN P, CATHALA F, GAJDUSEK DC: Creutzfeldt- Jakob disease in France: III. Epidemiological study of 170 patients dving during the decade 1968-1977. Ann Neurol 1979;6:438-446

5. BRUTON CJ, BRUTON RK, GENTLEMAN SM, ROBERTS GW: Diagnosis and incidence of prion (Creutzfeldt- Jakob) disease: a retrospective archival survey with im- plications for future research. Neurodegeneration 1995; 4: 357-368

6. BUREAU OF THE CENSUS: Alphabetical Index of Indus- tries and Occupations. Washington (DC): US Depart- ment of Commerce, PHC80R3,1982

7. BURNETT CA, MAURER J, DOSEMECI M: Mortality by occupation, industry, and cause of death. 24 reporting states, 1984-1988. Cincinnati (OH): US Department of Health and Human Services, Centers for Disease Con- trol, National Institute for Occupation Safety and Health, 1997 (DHHS - NIOSH publication No 97- 114)


Creutzfeldt-Jakob disease e rischio occupazionale. Folia Medica 2000; 71:177-185

9. COLLINS S, LAW MG, FLETCHER A, et al: Surgical treatment and risk of sporadic Creutzfeldt-Jakob dis- ease: a case-control study. Lancet 1999; 353: 693-697

10. COUSENS SN, ZEIDLER M, ESMONDE TF, et al: Spo- radic Creutzfeldt-Jakob disease in the United King- dom: analysis of epidemiological surveillance data for 1970-96. BMJ 1997; 315:389-395

11. DAVANIPOUR Z, ALTER M, SOBEL E, et al: Transmissi- ble virus dementia: evaluation of a zoonotic hypothesis. Neuroepidemiology 1986; 5: 194-206

12. DAVANIPOUR Z, SMOAK C, BOHR T, et al: Death cer- tificates: an efficient source for ascertainment of Creutzfeldt-Jakob disease. Neuroepidemiology 1995; 14:1-6

13. DOSEMECI M, HAYES RB, VETTER R, et al: Occupa- tional physical activity, socioeconomic status, and risks of 15 cancer sites in Turkey. Cancer Causes Control 1993;4: 313-321

14. ESMONDE T, LUECK CJD, SYMON L, et al: Creutzfeldt- Jakob disease and lyophilised dura mater grafts: report of two cases. J Neurol Neurosurg Psychiat 1994; 56: 999-1000

15. FAGIH B, EISENBERG MJ: Reuse of angioplasty catheters and risk of Creutzfeldt-Jakob disease. Am HeartJ 1999; 137:1173-1178

16. GAJDUSEK DC: Infectious amyloids: subacute spongi- form encephalopathies as transmissible cerebral amyloi- doses. In Fields BN, Knipe D, Howley PM, et al (eds): Virology, 3rd ed. Philadelphia (PA): Lippincott-Raven, 1996:2851-2900

17. GORE SM: More than happenstance: Creutzfeldt- Jakob disease in farmers and young adults. Br Med J 1995; J.U:1416-1418

18. GREEN L: Manual for scoring socioeconomic status for research on health behavior. Public Health Rep 1970; 85: 815-827

19. HOFMAN A, WIENTJENS PWM: Epidemiological evi- dence concerning possible causal link. Br Med J 1995; 311:1418-1419

20. 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

21.LANG CJ, HECKMANN JG, NEUNDORFER B: Creutzfeldt-Jakob disease via dural and corneal trans- plants. J Neurol Sd 1998; 160:128-139

22. LASK.E C, GEFELLER 0, PFAHLBERG A, et al: The ef- fect of stress on the onset and progression of Creutzfeldt-Jakob disease: results of a German pilot case-control study. EurJ Epidemiol 1999; 15: 631-635

23. MASTERS CL, HARRIS JO, GAJDUSEK DC, et al: Creutzfeldt-Jakob disease: patterns of worldwide occur- rence and the significance of familial and sporadic clus- tering. Ann Neurol 1979; 5:177-188

24. MASULLO C, POCCHIARI M, NERI G, et al. A retro- spective study of Creutzfeldt-Jakob disease in Italy (1972-1986). EurJ Epidemiol 1988; 4: 482-487

25. MITROVA E, BELAY G: Creutzfeldt-Jakob disease in health professionals in Slovakia. Eur J Epidemiol 2000; 16: 353-355

26. NAKAMURA Y, ASO E, YANAGAWA H: Relative risk of Creutzfeldt-Jakob disease with cadaveric dura trans- plantation in Japan. Neurology 1999; 53:218-220

27. NAKAMURA Y, OKI I, TANIHARA S, et al: A case-con- trol study of Creutzfeldt-Jakob disease in Japan: trans- plantation of cadaveric dura mater was a risk factor. J Epidemiol 2000; 10: 399-402

28. PLAITAKIS A, VISKADOURAKI AK, TZAGOURNISSAKIS M, et al: Increased incidence of sporadic Creutzfeldt- Jakob disease on the island of Crete associated with a high rate of PRNP 129-methionine homozygosity in the local population. Ann Neurol 2001; 50:227-233

29. PRICHARD J, THADANI V, KA.LE R, et al: Rapidly pro- gressive dementia in a patient who received a cadaveric dura mater graft. MMWR Morb Mortal Wkly Rep 1987; 36:49-50

30. PRUSINER SB: Novel proteinaceous infectious particles cause scrapie. Science 1996; 216:136-144

31. PRUSINER SB: Prions. In Fields BN, Knipe DM, How- ley PM, et al (eds): Virology, 3-' ed. Philadelphia (PA): Lippincott-Raven, 1996: 2901-2950

32. PRUSINER SB, HSIAO KH: Human prion diseases. Ann Neurol 1994; 35: 385-395

33-RICKETTS MN, CASHMAN NR, STRATTON EE, ElSAADANY S: Is Creutzfeldt-Jakob disease transmitted in blood? Emerg Infect Dis 1997; 3:155-163

34. RUTALA WA, WEBER DJ: Creutzfeldt-Jakob disease:



recommendations for disinfection and sterilization. Clin Infect Dis 2001; 32:1348-1356

35. SMITH PEM, ZEIDLER M, IRONSIDE JW, et al: Creutzfeldt-Jakob disease in a dairy farmer. Lancet 1995;346: 898

36.TAYLOR DM: The effect of formic acid on BSE and scrapie infecrivity in fixed and unfixed brain tissue. Vet Microbiol 1997; 58:167-174

37. THE EUROCJD GROUP: Genetic epidemiology of Creutzfeldt-Jakob disease in Europe. Rev Neurol 2001; 157: 633-637

38. THE NATIONAL CJD SURVEILLANCE UNIT: Creutzfeldt-Jakob Disease surveillance in the UK. Sixth Annual Report 1997. London (UK): Department of In- fectious and Tropical Disease, London School of Hy- giene and tropical Medicine, 1997

39. THE NATIONAL CJD SURVEILLANCE UNIT: Creutzfeldt-Jakob Disease surveillance in the U.K. Tenth Annual Report 2001. London (UK): Department of In- fectious and Tropical Disease, London School of Hy- giene and tropical Medicine, 2001

40. TYLER KL: Risk of human exposure to bovine spongi- form encephalopathy. Br MedJ 1995; 311:1420-1421

41. VAMVAKAS EC: Risk of transmission of Creutzfeldt- Jakob disease by transfusion of blood, plasma, and plas- ma derivatives. J Clin Apheresis 1999; 14:135-143

42. VAN DUIJN CM, DELASNERIE-LAUPETRE N, MASULLO C, et al: Case-control study of risk factors of Creutzfeldt-Jakob disease in Europe during 1993-95. European Union (EU) Collaborative Study Group of Creutzfeldt-Jakob disease (CJD). Lancet 1998; 351: 1081-1085

43. WARD HJ, EVERINGTON D, CROES EA, et al: Sporadic Creutzfeldt-Jakob disease and surgery; a case-control study using community controls. Neurology 2002; 59: 543-548

44. WEIS J, KRETZSCHMAR HA, WINDL 0, et al: Fatal spongiform encephalopathy in a patient who had han- dled animal feed. Lancet 1996; 348:1240

45. WIENTJENS DPWM, DAVANIPOUR Z, HOFMAN A, et al: Risk factors for Creutzfeldt-Jakob disease: a reanaly- sis of case-control studies. Neurology 1996; 46: 1287- 1291

46. WILL RG, IRONSIDE JW, ZEIDLER M, et al: A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996;347: 921-925

47. WORLD HEALTH ORGANIZATION CONSULTATION GROUP: Public health issues and clinical and neurologi- cal characteristics of the new variant of Creutzfeldt- Jakob disease and other human and animal transmissi- ble spongiform encephalopathies: memorandum from two WHO meetings. Bull World Health Organ 1996; 74: 453-463

48. YOUNG GR, FLETCHER NA, ZEIDLER M, et al: Creutzfeldt-Jakob disease in a beef farmer. Lancet 1996; 348: 610-611

49. ZERR I, BRANDEL JP, MASULLO C, et al: European sur- veillance on Creutzfeldt-Jakob disease: a case-control study for medical risk factors. J Clin Epidemiol 2000; 53: 747-754



Monday, January 17, 2011

Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice

Thursday, December 22, 2011

Risk of Prion Disease Transmission through Bovine-Derived Bone Substitutes: A Systematic Review Clin Implant Dent Relat Res. 2011 Dec 15. doi: 10.1111/j.1708-8208.2011.00407.x. [Epub ahead of print]

Saturday, December 3, 2011

Candidate Cell Substrates, Vaccine Production, and Transmissible Spongiform Encephalopathies

Volume 17, Number 12—December 2011

Friday, December 23, 2011

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

Volume 18, Number 1—January 2012 Dispatch

Saturday, December 3, 2011

Isolation of Prion with BSE Properties from Farmed Goat Volume 17, Number 12—December 2011

Monday, July 18, 2011

Impact of Being Placed at Risk of Creutzfeldt-Jakob Disease: A Qualitative Study of Blood Donors to Variant CJD Cases and Patients Potentially Surgically Exposed to CJD

Tuesday, March 29, 2011


Wednesday, June 29, 2011

TSEAC Meeting August 1, 2011 donor deferral ...

Monday, October 10, 2011 EFSA Journal 2011 The European Response to BSE: A Success Story


EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.


see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

Wednesday, June 15, 2011

Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor

Wednesday, March 31, 2010

Atypical BSE in Cattle

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

Thursday, August 12, 2010

Seven main threats for the future linked to prions

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.

Second threat


Saturday, November 19, 2011

Novel Prion Protein in BSE-affected Cattle, Switzerland


Saturday, December 3, 2011

Isolation of Prion with BSE Properties from Farmed Goat Volume 17, Number 12—December 2011

Saturday, June 25, 2011

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

"BSE-L in North America may have existed for decades"

Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.


The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...


When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures. This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.

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

Saturday, July 23, 2011


Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU


Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR>

Prion disease update 2010 (11) PRION DISEASE UPDATE 2010 (11)

October 2009 O.11.3 Infectivity in skeletal muscle of BASE-infected cattle

Silvia Suardi1, Chiara Vimercati1, Fabio Moda1, Ruggerone Margherita1, Ilaria Campagnani1, Guerino Lombardi2, Daniela Gelmetti2, Martin H. Groschup3, Anne Buschmann3, Cristina Casalone4, Maria Caramelli4, Salvatore Monaco5, Gianluigi Zanusso5, Fabrizio Tagliavini1 1Carlo Besta" Neurological Institute,Italy; 2IZS Brescia, Italy; 33FLI Insel Riems, D, Germany; 4CEA-IZS Torino, Italy; 5University of Verona, Italy

Background: BASE is an atypical form of bovine spongiform encephalopathy caused by a prion strain distinct from that of BSE. Upon experimental transmission to cattle, BASE induces a previously unrecognized disease phenotype marked by mental dullness and progressive atrophy of hind limb musculature. Whether affected muscles contain infectivity is unknown. This is a critical issue since the BASE strain is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible.

Objectives: To investigate the distribution of infectivity in peripheral tissues of cattle experimentally infected with BASE. Methods: Groups of Tg mice expressing bovine PrP (Tgbov XV, n= 7-15/group) were inoculated both i.c. and i.p. with 10% homogenates of a variety of tissues including brain, spleen, cervical lymph node, kidney and skeletal muscle (m. longissimus dorsi) from cattle intracerebrally infected with BASE. No PrPres was detectable in the peripheral tissues used for inoculation either by immunohistochemistry or Western blot.

Results: Mice inoculated with BASE-brain homogenates showed clinical signs of disease with incubation and survival times of 175±15 and 207±12 days. Five out of seven mice challenged with skeletal muscle developed a similar neurological disorder, with incubation and survival times of 380±11 and 410±12 days. At present (700 days after inoculation) mice challenged with the other peripheral tissues are still healthy. The neuropathological phenotype and PrPres type of the affected mice inoculated either with brain or muscle were indistinguishable and matched those of Tgbov XV mice infected with natural BASE.

Discussion: Our data indicate that the skeletal muscle of cattle experimentally infected with BASE contains significant amount of infectivity, at variance with BSE-affected cattle, raising the issue of intraspecies transmission and the potential risk for humans. Experiments are in progress to assess the presence of infectivity in skeletal muscles of natural BASE.

2011 Monday, September 26, 2011

L-BSE BASE prion and atypical sporadic CJD


Saturday, June 18, 2011

Self-propagation and transmission of misfolded mutant SOD1 Prion or Prion-like phenomenon?

Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011




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