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Sporadic CJD in the UK: 1970-96
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Sporadic CJD in the UK: analysis of epidemiological surveillance data for 1970-96

BMJ No 7105 Volume 315  Saturday 16 August 1997
S N Cousens, M Zeidler, T F Esmonde, R De Silva, J W Wilesmith, P G Smith, R G Will
During 1970-96 there was an increase in the number of sporadic cases of CJD recorded yearly in England and Wales. The greatest increase was among people aged over 70. There was a statistically significant excess of cases among dairy farm workers and their spouses and among people at increased risk of contact with live cattle infected with bovine spongiform encephalopathy. During 1994-6 there were six deaths from sporadic CJD in the UK in patients aged under 30.

The increase in the incidence of sporadic CJD and the high incidence in dairy farmers in the UK may be unrelated to bovine spongiform encephalopathy. The most striking change in the pattern of CJD in the UK after the epidemic of bovine spongiform encephalopathy is provided by the incidence in a group of exceptionally young patients with a consistent and unusual neuropathological profile. The outcome of mouse transmission studies and the future incidence of the disease in the UK and elsewhere, will be important in judging whether the agent causing bovine spongiform encephalopathy has infected humans.

Introduction

The UK National CJD Surveillance Unit was set up in May 1990 after recognition of the epidemic of bovine spongiform encephalopathy in the late 1980s.(1) If bovine spongiform encephalopathy infects humans it was considered most likely to result in disease manifestations similar to those of CJD and that some or all of the following phenomena might be observed: (a) an increase in the overall incidence of CJD in the UK; (b) an excess of cases in groups most likely to have high exposure to the causative agent of bovine spongiform encephalopathy; (c) a change in the epidemiological pattern of CJD, such as a change in the age distribution; (d) a change in the clinical or neuropathological characteristics of CJD. The identification in 1996 of a group of comparatively young patients with CJD characterised by unusual clinical and neuropathological features(2) led the Spongiform Encephalopathy Advisory Committee to advise the UK government that "the most likely explanation at present is that these cases are linked to exposure to BSE."(3)

We present data on age specific changes in the incidence of CJD in the UK since 1970 and examine the incidence rates of the disease since 1990 in groups who might have been occupationally exposed to the causative agent of bovine spongiform encephalopathy.

Methods

Surveillance of CJD
A series of studies has attempted to identify all cases of CJD occurring in England and Wales since 1970 and in the UK since 1985. Methods of case ascertainment have been described.(2,4) Briefly, cases of CJD occurring in England and Wales during 1970-9 were identified retrospectively at the end of that period(5) and prospective surveillance instituted to detect cases during 1980-4.(6) Prospective ascertainment of cases, extended to cover the whole of the UK, was reinstituted in May 1990 and is continuing. Cases occurring in the UK between 1985 and April 1990 were identified retrospectively.

Case ascertainment has been based throughout on direct notification of cases and on death certificates. Neurologists, neuropathologists, and neurophysiologists are asked to refer suspected cases of CJD, and the Office for National Statistics supplies death certificates coded under rubrics 339.9 and 781.7 (International Classification of Diseases, eighth revision (ICD-8)) and 046.1 and 331.9 (ICD-9). A few cases are referred by other routes.

Since May 1990 suspected cases have been seen, when possible, by a neurologist from the national surveillance unit and a close relative has been interviewed to collect epidemiological information, including the current and previous occupations of the patient.

Case definition
The diagnostic criteria for CJD have been essentially the same since surveillance began in 1970.(7) In summary, classification as a definite case requires neuropathological confirmation of spongiform change, or (since 1993) immunocytochemical confirmation of the presence of prion protein, or identification of scrapie associated fibrils on electron microscopy. Currently about 70% of patients with suspected CJD come to necropsy. In the absence of neuropathological investigation patients are classified as probable cases of CJD if they present with progressive dementia, a typical electroencephalogram, and at least two of the following: myoclonus; visual or cerebellar signs; pyramidal or extrapyramidal signs; akinetic mutism.

Cases are classified as iatrogenic when the patients have a known risk factor for accidental transmission (for example, pituitary hormone recipients). The criteria for inherited CJD have been updated to include information available from genetic analyses. Cases are now classified as inherited if the patients carry a disease specific mutation of the prion protein gene or have a history of probable or definite CJD in a first degree relative. Molecular biological data were available for 53% of cases identified since May 1990. All other cases are classified as sporadic. Probably during 1970-90 roughly half of inherited cases of CJD - that is, one or two a year - may have been classified as sporadic because genetic analyses were not carried out during the period.

Groups with potentially high occupational exposure
We do not know how or indeed if bovine spongiform encephalopathy is transmitted to humans. We identified three routes through which transmission might be hypothesised to occur.

Route 1 might be via contact with ruminant derived meat and bone meal contaminated by bovine spongiform encephalopathy (the likely source of the bovine epidemic).(8) Occupational groups identified to be at high risk of this exposure were workers on farms with cattle, pigs, poultry, sheep, or goats (as ruminant derived meat and bone meal may have been fed to these animals) and workers in feed mills producing meat and bone meal.

Route 2 might be via contact with live cattle infected with bovine spongiform encephalopathy. Occupational groups identified to be at high risk of this exposure were workers on farms with cattle, veterinarians, and abattoir workers. Three different populations of farm workers with increasing likelihood of exposure to live infected cattle were identified - namely, workers on all farms with cattle (dairy or beef herds); workers on farms with dairy cattle (the incidence of bovine spongiform encephalopathy has been much higher in dairy herds)(9); workers on dairy or beef farms with a confirmed case of bovine spongiform encephalopathy.

Route 3 might be via contact with brain or spinal cord from dead infected cattle. Occupational groups identified to be at high risk of this exposure were veterinarians, abattoir workers, workers in rendering plants, and butchers. Though cattle may be slaughtered on farms by licensed personnel and dressed by farmers, we have no evidence that this is widespread and farmers were therefore excluded from this occupational group.

The numbers of workers on different types of farms during 1990-4 were obtained from the annual agricultural censuses for England and Wales, Northern Ireland, and Scotland (1990-5). Data on the numbers of workers on farms affected by bovine spongiform encephalopathy were obtained by linking agricultural census data with the database on the disease held at the Central Veterinary Laboratory. The number of veterinarians, butchers, and meat cutters in Great Britain was estimated from the 10% sample of the 1991 census by using the recommended conversion factor of 10.16. The number of abattoir workers could not be derived from published census data for Great Britain, but information on these workers was provided by the Ministry of Agriculture, Fisheries and Food.

Data for Northern Ireland on veterinarians and on workers employed in the slaughtering of animals and the production of meat for 1993 were provided by the Department of Economic Development, Belfast. We could not derive the number of workers in rendering plants or feed mills producing meat and bone meal from published census data for Great Britain. However, the numbers of workers in these groups are small compared with the number of farm workers (see below) and their exclusion from calculation of the expected number of cases is therefore of no consequence. (The number of feed mill workers is estimated at about 3,000 (UK Agricultural Supply Trade Association, personal communication, 1996).

Expected numbers of cases in different occupational groups
Expected numbers of deaths from CJD between 1 May 1990 and 31 December 1996 were calculated by multiplying age specific and sex specific death rates for the UK population by the estimated numbers of people in the different occupational groups. The age and sex distribution of farm workers was assumed to follow that reported for farm workers in England and Wales in the European Commission's structure survey of 1990. The age and sex distributions of veterinarians and of butchers and meat cutters were assumed to follow those of the wider occupational groups within which they were classified in the 1991 census.

Observed and expected numbers of cases were compared in the assumption that the observed number of cases followed a Poisson distribution.

Results

Between 1 January 1970 and 31 December 1996, 708 definite and probable cases of CJD were identified. Five were in patients alive on 31 December 1996. In all, 540 (76%) cases were classified as definite. Twenty three cases were classified as iatrogenic and 23 as inherited, both of which groups were excluded from analysis. Among the 662 sporadic cases, 15 were of the variant form of the disease.

Distribution of cases by age, sex, and time period
In England and Wales the yearly number of deaths from CJD increased from around 10 at the beginning of the 1970s to around 40 in the 1990s (fig 1). No increase in yearly numbers of deaths was evident for Scotland and Northern Ireland after 1985 (fig 1).


Fig 1: Yearly numbers of deaths from CJD in England and Wales during 1970-96 and in Scotland and Northern Ireland during 1985-96 (data exclude known iatragenic and inherited cases). Horizontal lines represent numbers of deaths corresponding to yearly death rates of 0.5/million (lower) and 1.0/million (upper).

Figure 2 shows the average yearly age specific and sex specific death rates over the study period. Below 40 years of age, death rates were extremely low (<0.1/million yearly). Death rates increased substantially in the 50-59 year age group and reached a peak of around 2.0/million yearly in the 60-69 year age group before declining in people aged 70 and over.
Fig 2: Age and sex specific average yearly death rates from CJD in UK during 1970-96.

Table 1 shows the numbers of deaths in 10 year age groups for each two year period from 1970 to 1996. Mortality from CJD increased substantially over the period in patients aged 70 and over and by successively smaller proportions in those aged 60-69 and 50-59 (fig 3; table 2). The increase in patients aged 40-49 years was not significant (P=0.27). Under the age of 40 numbers of cases were small, but of the seven patients who died under the age of 30, six had onset of the disease after 1 January 1994. All six died in 1995 or 1996.
Fig 3: Trends in age specific death rates from CJD in England and Wales during 1970-96. For age group 40-49 years death rates for 1972-3 and 1984-5 are not plotted as there were no deaths in this age group in the periods.

Table 1 - Numbers of deaths from CJD in 10 year age groups for each two year period in England and Wales (from 70) and UK* (from 85)
Age group (years)Two year periodTotal†
70-172-374-576-778-980-182-384-586-788-990-192-394-596†
10-1900000100000011 (1)3 (1)
20-2900000000000013 (0)4 (0)
30-3910022114101014 (0)18 (0)
40-4920211210322344 (0)27 (0)
50-5979116111312105131812144 (1)145 (1)
60-6991310221724202822172838328 (2)288 (2)
70 and over222494121618179293712 (0)173 (0)
Total2124253540454658494958829036 (4)658 (4)
Table excludes cases known to be iatrogenic or inherited.
*UK includes cases from Scotland and Northern Ireland.
†Figures in parentheses are numbers of patients alive on 1 January 97.

Table 2 - Rate of increase in mortality from sporadic CJD by age group
Age group (years) Average % increase in mortality over two year period (95% CI) P value
40-496.6 (-4.8 to 19.5)0.27
50-594.1 (-0.1 to 8.8)0.08
60-697.3 (3.9 to 10.8)<0.001
70 and under21.3 (15.4 to 27.5)<0.001

Sporadic disease in groups with potential occupational exposure
Six cases of sporadic CJD (five definite, four in men) were identified from 1 May 1990 in people whose occupation at disease onset was in one of the groups identified above. Four have been the subject of case reports.(10-13) Ages at death in the six cases were 54, 54, 59, 61, 64, and 64 years. All five patients subjected to neuropathological investigation showed changes typical of CJD. None showed the "florid" plaques characteristic of the variant form of the disease.(2) The sixth, probable case followed a clinical course typical of sporadic CJD with a characteristic electroencephalogram.

Four of the six patients lived or worked on dairy farms (on three of which there had been confirmed cases of bovine spongiform encephalopathy), and two lived or worked on farms with beef suckler herds (one with a confirmed case of bovine spongiform encephalopathy). Two of the six cases were in spouses of farmers. All patients had lived or worked on farms throughout their working lives. Table 3 shows the distribution of these cases by occupational group. There was a significant excess of cases among animal farm workers (6 observed, 2.4 expected; P=0.03). All these cases were in cattle farmers, four of whom worked on farms with a case of bovine spongiform encephalopathy. This excess of cases was highly significant (4 observed, 0.58 expected; P=0.003). Table 4 shows the distribution of observed and expected cases by hypothesised route of transmission. There was an excess of cases among workers potentially exposed to ruminant derived meat and bone meal and among workers exposed to live cattle infected with bovine spongiform encephalopathy. Two cases among farmers were on farms without a case of bovine spongiform encephalopathy compared with an expected number of 1.78 (P=0.5).

Table 3 - Distribution of expected and observed cases of CJD among occupational groups potentially at increased risk of infection with bovine spongiform encephalopathy
Occupational groupNo of subjects in group*No of cases of CJD 1 May 1990 to 31 December 1996Yearly incidence/millionP value†
ExpectedObserved
Farm workers on farms with cattle, pigs, poultry, sheep, or goats447,1622.3662.010.03
Farm workers on farms with cattle (dairy or beef)354,2421.8762.540.01
Farm workers on farms with dairy cattle149,4360.7944.020.01
Farm workers on farms with confirmed case of bovine spongiform encephalopathy109,6430.5845.470.003
Veterinarians8,2250.03001.0
Abattoir workers, butchers, meat cutters68,300‡0.15001.0
*Numbers given for farm workers include spouses and represent an average over period.
†P values indicate probability of obtaining observed number of cases or more under null hypothesis that there is no occupational risk of CJD.
‡Includes an estimated 48,300 butchers and meat cutters in Great Britain (1991 census), 12,400 staff employed in red meat slaughtering (Ministry of Agriculture, Fisheries and Food), and 7,600 staff employed in slaughtering animals and production of meat in Northern Ireland (Department of Economic Development, Belfast).

Table 4 - Distribution of expected and observed cases of CJD by hypothesised route of exposure to agent of bovine spongiform encephalopathy
Type of potential contact with agent of bovine spongiform encephalopathyNo of subjects exposed*No of cases of bovine spongiform encephalopathy 1 May 1990 to 31 December 1996Yearly incidence/millionP value†
ExpectedObserved
Contact with ruminant derived meat and bone meal (farm workers on farms with cattle, pigs, poultry, sheep, or goats)447,1622.3662.010.03
Contact with live cattle infected with bovine spongiform encephalopathy (farm workers on farms with confirmed case of bovine disease, veterinarians, abattoir workers)132,4080.6444.530.004
Contact with brain and spinal cord of dead cattle (butchers and meat cutters)68,3000.15001.0
*Numbers given for farm workers include spouses and represent an average over period.
†P values indicate probability of obtaining observed number of cases or more under null hypothesis that there is no occupational risk of CJD.

Discussion

In our introduction we identified four changes in the pattern of CJD that might occur if exposure to the bovine agent caused spongiform encephalopathy in humans. Arguably all of these changes may have occurred. There are, however, important caveats that inhibit clear interpretation of our findings.

The number of sporadic cases of CJD recorded in England and Wales has increased. During a period of prospective surveillance before the advent of bovine spongiform encephalopathy (1980-4) the yearly number of deaths from sporadic CJD in England and Wales averaged 24.8. During prospective surveillance after the epidemic of bovine spongiform encephalopathy (1990-6) the yearly number of deaths averaged 33.6. However, similar increases in the incidence of CJD have been observed in countries where the bovine disease is rare or absent (table 5).(14,15) These increases may reflect improved case ascertainment rather than real increases in incidence. It has long been suspected that the age distribution of CJD in the UK (fig 2) and elsewhere - with a decline in incidence in people over 70 - might reflect under ascertainment of cases in older age groups.(16) In the UK the greatest increase in incidence has been in people aged over 70. For many diseases case ascertainment is likely to be poorest among old people and best among age groups in which death from any cause is unusual. Thus aside from the recent increase in cases in young people, the age specific time trends suggest that improved ascertainment may explain much or all of the apparent rise in the incidence of CJD since 1970.

Table 5 - Incidence of CJD in countries other than UK over time
Country Yearly incidence/million
Chile:
1955-720.10
1973-70.31
1978-830.69
France:
1968-770.34
1978-820.58
1992-40.81
Germany:
1979-900.31
1993-40.68
United States:
1973-70.26
1986-80.83

We found significant excesses of cases of CJD among workers on dairy farms and on farms with a confirmed case of bovine spongiform encephalopathy. None of the six patients who might have been occupationally exposed to the agent of bovine spongiform encephalopathy presented with the variant form of CJD, which might indicate a different aetiology from the variant form. However, evidence from iatrogenic cases that route of infection may be a determinant of the clinical and pathological pattern of disease(17) means that we cannot exclude entirely the possibility that "occupational" cases and the variant form of the disease arise from exposure to the same agent by different routes. One possible explanation for the apparent excess risk among farmers is that case ascertainment of CJD in the UK has been better in this group than among other groups because of awareness of a possible link between the bovine and human diseases. Moreover, though the incidence of CJD among dairy farmers in the UK is higher than in the general population, it does not seem remarkable when compared with the incidence among dairy farmers in other European countries where bovine spongiform encephalopathy is rare or absent (table 6).(15) This suggests that dairy farmers may be at increased risk of CJD for reasons other than exposure to the causative agent of the bovine disease. We emphasise also that, though some farm workers seem to be at increased risk of CJDe compared with the general population, their absolute risk remains extremely low, the yearly incidence of the disease being well below 10 cases/million.

Table 6 - Incidence rates of CJD in dairy farmers in different European countries
Country Period No of cases Yearly incidence/million
France1992-444.8
Germany1993-423.8
Italy199329.4
Netherlands1993-400
United Kingdom1990-644.0

Our analyses are based on occupation at the time of disease onset, as national data are not available on the numbers of people ever employed in particular occupational groups. We therefore excluded from the analyses one patient who had worked in an abattoir for 10 months, six years before disease onset in 1995; one patient who had worked on a farm with dairy and beef herds until retiring in 1991, four years before disease onset in 1995; and one patient with the variant form of the disease who had worked as a butcher between 1985 and 1987. Another case of interest that was similarly excluded was of a man who transported meat and bone meal from an animal feed compounder to farms for many years up to 1991 but who changed his job before onset of CJD in 1993.

Cases with unusual features
During 1994-6, 10 cases of sporadic CJD occurred in the UK in patients under the age of 30. Based on past experience in the UK (two cases in the preceding 24 years) and elsewhere(2) this is unusual. That nine of these patients together with five others aged 30, 32, 34, 39, and 48 years at onset also exhibited a previously undescribed neuropathological pattern renders this finding even more remarkable and raises important questions. Were these cases really "new" or had similar cases occurred previously without being identified? If these cases were new why did they occur in the UK in the mid-1990s?

Bruton et al reviewed the Runwell Hospital Brain Archive and identified 19 cases of spongiform encephalopathy, only 11 of which had been diagnosed before death.(18) All the patients died before 1985, and none showed the neuropathological changes characteristic of the variant form of CJD. The authors suggested that prion diseases may be more common than supposed. Only about 4% of elderly patients dying with dementia come to necropsy.(19) Taken with our finding of a substantial increase over time in the number of cases identified in older age groups, it seems likely that some cases of CJD in this age group have been missed. To maintain the hypothesis that the phenomenon of cases in young people with striking neuropathological changes is not new requires that young people dying of progressive neurological disorders over the past several decades came to necropsy sufficiently rarely for such cases to have been missed entirely. Since 1979 about 46% of patients aged under 45 dying of dementias with which CJD might be confused have come to necropsy, with no evidence that necropsy rates have increased over that time.(19) Thus though we cannot exclude the possibility that such cases were missed, it seems to us an unlikely explanation.

If we accept for the present that these young cases are a new phenomenon, why did they appear in the UK in the mid-1990s? Bovine spongiform encephalopathy has been advanced as the most likely explanation.(3) Other workers have asked why in the absence of direct evidence of a link bovine spongiform encephalopathy should be singled out ahead of microwave ovens, high voltage power lines, or organophosphorous sheep dips.(20) These exposures are not confined to the UK and therefore seem less plausible explanations than bovine spongiform encephalopathy. The one case of the variant form of CJD reported in France(21) does not compromise the plausibility of the link with bovine spongiform encephalopathy. France has been one of the biggest markets for exported British beef, beef products, and cattle (B Schreuder, J Wilesmith, O Straub, personal communication, 1996).(22)

One argument against the plausibility of a link between bovine spongiform encephalopathy and the variant form of CJD is that the variant disease has been observed mainly in young people. The lack of cases in older age groups could be due to misdiagnosis, reduced susceptibility, or age related exposure to the agent.(2) That the variant form of the disease may have been missed in old people seems plausible but that it would be missed in patients in their late 40s and early 50s seems less so. That age related exposure explains the observed age distribution of the cases is also difficult to sustain, as the link between age and exposure would have to be very strong, and we have identified no exposure related to bovine spongiform encephalopathy that meets this condition.

In summary, the epidemiological data available suggest that the distribution of CJD in the UK population may be changing. Neuropathological data suggest that a new form of the disease may have appeared which could partly but not wholly explain the epidemiological anomalies observed. There is no direct evidence that links bovine spongiform encephalopathy with these changes, but recent observations accord with this hypothesis.(23,24) The results of transmission studies from human CJD cases to mice and the future incidence of CJD in the UK and elsewhere will be important in judging whether the causative agent of bovine spongiform encephalopathy has infected humans.

Hill et al have recently reported the findings of a Western blot analysis of protease resistant prion protein (PrPRES from five of the six farmers reported here.(25) On the basis of fragment size and glycoform ratio of this protein, all five were classified as having type I or type II PrPRES. These are types associated with the classical form of CJD and not with the variant form. These authors conclude that their results, in conjunction with the phenotype of these patients, do not support a link with occupational exposure to the agent of bovine spongiform encephalopathy.

Key Messages

  1. The overall incidence of CJD in the UK has increased in recent years.

  2. The largest increases have been in the oldest age groups and probably represent improved case ascertainment rather than a real change in incidence.

  3. The comparatively high incidence of CJD in dairy farmers in the UK is comparable to that observed in dairy farmers in countries where bovine spongiform encephalopathy is rare or absen.t

  4. The observation of a group of comparatively young patients with CJD characterised by unusual neuropathological features during 1994-6 remains unexplained.

  5. The results of mouse transmission studies and the future incidence of CJD in the UK and elsewhere will be important in judging whether the causative agent of bovine spongiform encephalopathy has infected human.

References

1 Wells G A H, Scott A C, Johnson C T, Gunning R F, Hancock R D, Jeffrey M, et al. A novel progressive spongiform encephalopathy in cattle. Vet Rec 1987;121:419-20.

2 Will R G, Ironside J W, Zeidler M, Cousens S N, Estibeiro K, Alperovitch A, et al. A new variant of CJD in the UK. Lancet 1996;347:921-5.

3 Spongiform Encephalopathy Advisory Committee. Statement. London, HMSO, 1996.

4 Cousens S N, Harries-Jones R, Knight R, Will R, Smith P G, Matthews W B. Geographical distribution of cases of CJD in England and Wales 1970-84. J Neurol Neurosurg Psychiatry 1990;53:459-65.

5 Will R G, Matthews W B. A retrospective study of CJD in England and Wales 1970-1979. I: clinical features. J Neurol Neurosurg Psychiatry 1984;47:134-40.

6 Harries-Jones R, Knight R, Will R G, Cousens S, Smith P G, Matthews W B. CJD in England and Wales, 1980-84: a case-control study of potential risk factors. J Neurol Neurosurg Psychiatry 1988;51:1113-9.

7 Will R G. Surveillance of prion diseases in humans. In: Baker H, Ridley R M, eds. Methods in molecular medicine: prion diseases. Totowa: Humana Press, 1996:119-37.

8 Wilesmith J W, Wells G A H, Cranwell M P, Ryan J M B. Bovine spongiform encephalopathy: epidemiological studies. Vet Rec 1988;123:638-44.

9 Wilesmith J W. Bovine spongiform encephalopathy: epidemiological factors associated with the emergence of an important new animal pathogen in Great Britain. Semin Virol 1994;5:179-87.

10 Sawcer S J, Yuill G M, Esmonde T F G, Estibeiro P, Ironside J W, Bell J E, et al. CJD in an individual occupationally exposed to BSE. Lancet 1993;341:642.

11 Davies P T G, Jahtar S, Ferguson I T, Windl O. Creutzfeldt-Jakob disease in an individual occupationally exposed to BSE. Lancet 1993;342:680.

12 Smith P E M, Zeidler M, Ironside J W, Estibeiro P, Moss T H. CJD in a dairy farmer. Lancet 1995;346:898.

13 Young G R, Fletcher N A, Zeidler M, Estibeiro K, Ironside J W. CJD in a beef farmer. Lancet 1996;348:610-1.

14 Brown P, Cathala F, Raubertas R F, Gajdusek D C, Castaigne P. The epidemiology of CJD: conclusions of a 15-year investigation in France and review of the world literature. Neurology 1987;37:895-904.

15 National CJD Surveillance Unit. Fourth annual report to the Department of Health. Edinburgh: NCJDSU, 1995.

16 Will R G, Matthews W B, Smith P G, Hudson C. A retrospective study of CJD in England and Wales. II: Epidemiology. J Neurol Neurosurg Psychiatry 1986;49:749-55.

17 Bell J E, Ironside J W. Neuropathology of spongiform encephalopathies in humans. Br Med Bull 1993;49:738-77.

18 Bruton C J, Bruton R K, Gentleman S M, Roberts G W. Diagnosis and incidence of prion (Creutzfeldt-Jakob) disease: a retrospective archival survey with implications for further research. Neurodegeneration 1995;4:357-68.

19 Aylin P, Rooney C, Drever F, Coleman M. Increasing mortality from CJD in England and Wales since 1979: ascertainment bias from increase in post-mortems? Popul Trends 1996;85:34-8.

20 Wickham A. CJD and BSE: advisory committee's conclusion was based on "absence of any credible alternative." BMJ 1996;312:1038.

21 Chazot G, Broussolle E, Lapras CI, Blättler T, Aguzzi A, Kopp N. New variant of CJD in a 26-year-old French man. Lancet 1996;347:1181.

22 Meyer L A. Impact of BSE on UK bone-in beef exports and UK beef fatstock prices. Wageningen: Wageningen Agricultural University, 1996. (MSc thesis.)

23 Lasmézas C I, Deslys J-P, Demaimay R, Adjou K T, Lamoury F, Dormont D. BSE transmission to macaques. Nature 1996;381:743-4.

24 Collinge J, Sidle K C L, Meads J, Ironside J, Hill A F. Molecular analysis of prion strain variation and the aetiology of "new variant" CJD. Nature 1996;383:685-90.

25 Hill A F, Will R G, Ironside J, Collinge J. Type of prion protein in UK farmers with Creutzfeld-Jakob disease. Lancet 1997;350:188.

Age related exposure of patients to the agent of BSE should not be downplayed

BMJ No 7105 Volume 315 16 August 1997
Sheila M Gore
There have been two periods of prospective surveillance of CJD in the UK - during 1980-4, covering England and Wales only, and from 1 May 1990, covering the whole of the UK. Approximating these, table 1 summarises by age groups the cases reported for 1980-5 and 1990-5, together with the respective reference populations. Case ascertainment in patients under 70 was 20% higher in 1990-5 than in 1980-5 but more than doubled for patients aged 70 and over; in 1990-5, 2.16 cases per million population aged 70 and over were notified yearly. Comparison of rates of CJD among patients aged 70 and over from comparable prospective surveillance studies elsewhere in the European Union and internationally could give reassurance that there were no reasons other than differentially enhanced ascertainment which accounted for the doubling - such as enhanced dietary exposure to the causative agent of bovine spongiform encephalopathy at older ages in the UK. More generally, because the incidence of CJD varies so greatly with age group, it makes little sense epidemiologically to present international comparisons of incidence unless they are age group specific or age standardised. I therefore endorse the decision in France that routine reporting of sporadic cases and the variant forms of CJD should be by 10 year age groups.(1)

With only one sporadic case of CJD in a patient under 40 diagnosed yearly in the UK before 1996, how many suspected cases in patients under 40 were actually referred to the surveillance unit in 1980-5 and 1990-5, of whom 11 were diagnosed as having sporadic CJD? And did the referral pattern change in 1996 because of the emergence of the variant form of the disease? Partial answers are given in a recent letter in the Lancet but this concerns a broader age group (under 50 at referral to the surveillance unit) and gives data for April 1996 to February 1997 only.(2)

Table 1 - Distribution of cases of Creutzfeldt-Jakob disease by age group and surveillance period
Age group (years)1980-5 England and Wales 1990-5 United KingdomRelative rate
Reference population (millions)Cases of Creutzfeldt-Jakob diseaseReference population (millions)Cases of Creutzfeldt-Jakob disease
NoYearly incidence/millionNoYearly incidence/million
10-3922.14070.0523.32540.031.17
40-495.73430.097.54790.20
50-595.453351.075.964441.231.15
60-695.080722.365.663982.881.22
70 and over5.308321.005.796752.162.15

In discussing the 14 confirmed cases of the variant form of CJD, all but one occurring in patients under 40 at the onset of clinical illness, Will et al downplay age related exposure to the agent of bovine spongiform encephalopathy as an explanation for the observed age distribution. They identified no exposure related to the bovine disease that was sufficiently strongly related to age. However, consumption of certain foods is strongly age related (p 404)(3). For example, in 1986-7, burgers and kebabs were consumed by 45% of 16-24 year olds but by only 13% of 50-64 year olds. By contrast, the consumption of beef or even sausages is not age related.(4)

Let us turn now from young adults to farmers. Will et al confirm that the occurrence of sporadic CJD in farmers is more than happenstance.(5) Molecular marker studies of bovine spongiform encephalopathy reported by Collinge et al effectively proved that the variant form of CJD is caused by the same agent that causes the bovine disease.(6) Hence as well as transmission studies with brain tissue taken at necropsy from farmers dying of CJD, molecular marker studies will be important in determining whether some of the cases in farmers were likely to have been due to occupational exposure to the infectious agent in cattle. It is worth recalling that in July 1996 (that is, before Collinge's work was reported) the degree of belief in the proposition that bovine spongiform encephalopathy causes the variant form of CJD averaged 5.4 (SD 2.8) on a scale of 0 (nil belief) to 10 (absolute certainty).(7)

Will et al report that in addition to the six cases of CJD in lifelong farmers, there had been three other confirmed cases since 1 May 1990 in people who belonged formerly to the occupational group comprising abattoir workers, butchers, meat cutters, and rendering plant workers. This occupational group together with veterinarians accounted for no more than s = 78,000 workers yearly. The "ever employed" person years in this occupational group to be counted in the surveillance period 1990-5 depend on turnover of staff. If all 78,000 remained in the occupational group throughout 1981-95 they would contribute only 6s = 6 x 78,000 = 0.468 million person years to the surveillance period 1990-5. If two thirds of employees stayed for 15 years, one sixth were replaced every year, and one sixth turned over after three years, then the person years contribution would increase considerably. Serious consideration needs to be given to the proper estimation of "ever employed" and "continuously employed" denominators if full use is to be made of occupational histories collected in cases of Creutzfeld-Jakob diseases.

References

1 Alperovitch A, Brendel J B, Chalclain J, Delasncrio-Laupretre N, Deslys J-P, Dormont D, et al. Situation en France. Incidence de la maladie de Creutzfeldt-Jakob en France. Bull Epidemiol Hebdom 1996;48:207-8.

2 Will R G, Knight R S G, Zeidler M, Stewart G, Ironside J W, Cousens S N, et al. Reporting of suspect new variant Creutzfeldt-Jakob disease. Lancet 1997;349:847-8.

3 Gore S M, Bingham S, Day N. Age related dietary exposure to meat products from British dietary surveys of teenagers and adults in the 1980s and 1990s. 1997;315:404-5.

4 Gregory J R, Foster K, Tyler H, Wiseman M. Dietary and nutrition survey of British adults, 1986-7. London: HMSO, 1990.

5 Gore S M. More than happenstance: Creutzfeld-Jakob disease in farmers and young adults. BMJ 1995;311:1416-8.

6 Collinge J, Sidle K C L, Meads J, Ironside J, Hill A F. Molecular analysis of prion strain variation and the aetiology of "new variant" CJD. Nature 1996;383:685-90.

7 Gore S M. Address to the Parliamentary and Scientific Committee. More than happenstance: CJD in farmers and young adults. Sci Parliament 1996;53:2-3.

Young people consumed more burgers than older people in 1980s and 1990s

BMJ editorial 16 Aug 1997
The announcement in 1996 of cases of a new form of Creutzfeldt-Jakob disease in young patients in the United Kingdom and the possibility that they resulted from exposure to the causative agent of bovine spongiform encephalopathy received worldwide attention. Cousens et al (p 389) analysed data on Creutzfeldt-Jakob disease in the United Kingdom during 1970-96 to see if other changes had occurred that could be linked to bovine spongiform encephalopathy, but point out that many cases were in elderly people and thus might be due to better ascertainment and that dairy farmers throughout Europe have a high incidence. The cause of the variant form of Creutzfeldt-Jakob disease in young people remains unestablished, and the authors cite its future incidence and mouse transmission studies as important in judging whether the agent infecting cattle has infected humans.

In a commentary accompanying the paper by Cousens et al, Gore argues that age analysis of cases is important, and a paper by Gore et al analyses age trends in consumption of mechanically recovered meat - that most likely to have harboured the agent responsible for bovine spongiform encephalopathy (p 395). A dietary survey of British adults in 1986-7 showed an age gradient in the proportions of people eating burgers and kebabs (and the amount they ate), from 45% of those aged 18-24 to 13% of those aged 50-64. No differences occurred in the consumption of sausages and beef. They argue that such data may be relevant given the fact that new variant Creutzfeldt-Jakob disease occurs in young people.

BSE threatens drugs in European Union

BMJ No 7105 Volume 315 Letters Saturday 16 August 1997
 Alan Earl-Slater 
Editor,
While the debates about bovine spongiform encephalopathy periodically have a high profile in public health, food safety, and agricultural and political environments, the pharmaceutical environment is now becoming seriously entangled in the web of controversy. On 20 February this year the pharmaceutical council of the European parliament accepted the European Commission's proposed revisions to directive 75/18/EEC.

If the revisions are accepted by the European Union's Council of Ministers it will mean that drugs for human consumption that have bovine, ovine, or caprine ingredients, or ingredients derived from such, will (with one exception) not be allowed on any member state's market after 31 December. Over 200 drugs with gelatin capsules will be affected, as will specific products such as HibTITER (Haemophilus influenzae type b vaccine), Hyalase (hyaluronidase), and Hypurin (insulin).(1)

The only exception to the ban will be drugs with such ingredients that have or secure a pan-European Union product licence through the European Medicines Evaluation Agency's centralised route and for which no alternative drug is available. This escape route shows another aspect of the growing importance of the pan-European Union drug licensing system.(2)

On 10 June this year Emma Bonino, the commissioner for fisheries, consumer policy, and the European humanitarian office, announced the creation of another committee of the European Union, the scientific steering committee. This will act as the supreme source of expertise for the commission and offer excellence, independence, and transparency.

The first task for the scientific steering committee must be to make available the scientific evidence and rationale underpinning the decision to revise directive 75/18/EEC. If there is a scientific basis for the policy the committee should, being excellent and independent, produce it for all to see. The more obvious reason for the commission's actions is that the European parliament had earlier threatened by 422 votes to 49 to force the commission to resign in a body if it did not act on the crises over bovine spongiform encephalopathy. Whether the emerging responses are justified or prudent remains questionable. Who is going to benefit from this malaise in policy and this lack of evidence based decision making: the millions of consumers of meat, jellies, sweets, and drugs?(3-5)

References

 1 Association of the British Pharmaceutical Industry. Compendium of data sheets and
 summaries of product characteristics. London: ABPI, 1996. 

 2 Earl-Slater A. Recent developments in regulating the pharmaceutical business in the EU.
 European Business Review 1996;96(1):17-25. 

 3 Belcher P, Mossialos M. Health priorities for the European intergovernmental conference.
 BMJ 1997;314:1637-8. (7 June.) 

 4 Coghlan T. New Labour, new Europe. BMJ 1997;314:1506. (24 May.) 

 5 Davis P. Managing medicines: public policy and therapeutic drugs. Buckingham: Open
 University Press, 1997. 

Scientists who inflame public anxieties must share responsibility for resulting panic

1996 BMJ MICHAEL FITZPATRICK ... General practitioner

EDITOR - Recent editorials on the danger of bovine spongiform encephalopathy causing Creutzfeldt-Jakob disease in humans confirm that academic scientists are as much in the grip of the irrationality of the mad cow panic as is the public.[i,ii] a Paul Brown recalls his judgment of last November that the available evidence suggested "a negligible risk to humans,"[iii] only to confess that it now appears that I was wrong."[i] However, he adduces no new evidence to justify this about turn, simply repeating the now familiar refrain that "no better explanation is presently forthcoming."

Being unable to advance a better explanation than that offered by a hypothesis for which there is only the weakest circumstantial backing is a dubious basis for endorsing that hypothesis. Yet, within a few sentences, Brown is raising the spectre of "a potential medical catastrophe." If an eminent scientist can swing in four months from characterising bovine spongiform encephalopathy as a negligible risk to warning of potential catastrophe is it any wonder that the public is confused and frightened?

With rhetorical flourish, Sheila M Gore demands, "let us have done with misleading the profession, the public, and the press" and insists that "all evidence must be quantified."[ii] As there is no evidence for a link between bovine spongiform encephalopathy and Creutzfeldt-Jakob disease it cannot be quantified; what is misleading is to imply that the link is something more than the weakest of hypotheses. Yet this is exactly the effect of the statement that there is "no better explanation" or that this is "the most likely cause. Echoed in parliament and the press, such statements have fuelled the mad cow panic. Gore's powerful metaphors about British beef consumers continuing "to play Russian roulette" can only contribute to the hysteria.

Gore emphasises the need to learn the lessons of the AIDS crisis. Back in 1987 I argued that there was no evidence to justify the promotion of fears of an imminent explosion of HIV infection among heterosexuals in Britain.[iv] Now, nearly a decade later, we have a health scare not about a disease but about the possibility of a disease, Scientists who inflame public anxieties about uncommon or rare or possibly non-existent diseases (like bovine Creutzfeldt-Jakob disease) must take their share of the responsibility for the resulting panic and its consequences.

References

i. Brown P. Bovine spongiform encephalopathy and Creutzfeldt-Jakob disease. BMJ 1996 312,790-1 (30 March.)

ii. Gore S. Bovine Creutzfeldt-Jakob disease? BMJ 1996 312,790-1 (30 March.)

iii. Almond JW, Brown P, Gore SM, Hofman A, Wientjens DPWM, Ridley RM, et al. Creutzfeldt-Jakob disease and bovine spongiform encephalopathy: any connection? BMJ 1995;311:1415-21(25 November.)

iv. Fitzpatrick M. The truth about the AIDS panic. London. Junius, 1987.

Doctors and scientists must be able to communicate degree of risk...

JOHN HARRISON Senior lecturer in occupational medicine
EDITOR - The handling of the issue of bovine spongiform encephalopathy[i] is an example of the consequences of poor communication about risk. Risk management and the communication of risk are not new, and it is disappointing that the principles of the communication of risk have not been applied. The Environmental Protection Agency in the United States has published a set of rules and guidelines, most of which seem to have been ignored in the past few weeks[ii].' accept the public as a legitimate partner; listen to your audience; be honest, frank, and open; meet the needs of the media; speak clearly and with compassion; coordinate and collaborate with other credible sources; and plan carefully and evaluate performance.

Analysis of the problems encountered in terms of the sources of information on bovine spongiform encephalopathy and Creutzfeldt-Jakob disease, the means of communication, the messages that have been given, and the people receiving the information is revealing. There is a general lack of trust in the responsible authorities; there has been disagreement among scientific experts; the reporting of the issues in the media has dramatised events and emphasised the conflicts; and it has been difficult to explain the scientific uncertainties to a lay public that has inaccurate perceptions of risk and demands scientific certainty.

While the finger of blame will be pointed at the government, none of us can afford to be complacent. As doctors or scientists we are asked to give opinions about a range of issues, not all of which lie within our area of expertise. We will probably also be asked about issues that are at the boundaries of medical and scientific knowledge and about which considerable uncertainty exists. It is incumbent onus to be aware of all the arguments and to be able to communicate the levels of uncertainty associated with them in an understandable fashion. We need to work with the media so that we remain in control of the debates, and, above all, we must preserve our professional credibility' at a time when those around us are losing theirs.

References

i. Dillner L. BSE linked to new variant or CJD in humans. BMJ 1996;312:795 (30 March.)

ii. Cohrssen JJ, Covello VT. Risk analysis: a guide to principles and methods for analysing health and environmental risks Washington: National Technical Information Service, US Department of Commerce, 1989,

... but members of the public make up their own minds about risks

KD GUNASEKERA, AI HAPGOOD, EL HARVEY, TRM HAYFRON BENJAMIN, ... FIONA ADSHEAD
EDITOR - The government's recent statement on bovine spongiform encephalopathy has focused media interest on its potential impact on consumer behaviour.[i] The general public's response to media reports on "mad cow disease" and how this might have affected their behaviour already have not been well documented. In a survey among nurses 5% reported avoiding beef and a further 58% said that they would do so if cross species transmission was confirmed.[ii]

Before the government's most recent statement we interviewed 155 members of the general public in three south London boroughs to assess their knowledge of bovine spongiform encephalopathy and how this related to changes in beef consumption. Twenty one general practitioners also completed the questionnaire.

Overall knowledge of bovine spongiform encephalopathy was good, with 147 of the members of the general public being aware of the disease. Their assessment of the risk of Creutzfeldt-Jakob disease was accurate, with 129 saying that it was either rare or extremely rare and 120 correctly estimating the number of deaths in Britain each year as 50 or fewer.[iii] Altogether 134 reported that the media were their source of information, with only five having consulted their general practitioner.

Eighty one (55%) members of the public thought that humans could get the disease by eating cow products, compared with 12 (57%) general practitioners. Sixty (41%) members of the public and 14 (67%) general practitioners had reduced their beef consumption. The public tended to avoid all beef products, whereas general practitioners were more likely to refrain selectively from eating offal products (39 of the public avoided all beef and 21 were selective, compared with four and 10 general practitioners respectively; (chi-squared=6.2, df= I, P=0.01).

Generally the public were true to their beliefs and changed their behaviour accordingly. Forty (49%) of those who believed that transmission was possible had reduced their beef consumption, compared with 14 (29%) who were unsure about transmission and none who thought that transmission was impossible (chi-squared= 17.2, df=23 P=0.002).

We also identified a subgroup of 59 people who had consistently changed their diet in response to previous media reports, such as the scares over salmonella and listeria in food, Of these, 34 (58%) had decreased their beef intake, compared with only 25 (28%) who had not previously changed their behaviour (chi-squared= 12.6, df= 1, P=0.0004).

Thus, before the recent statements, the general public seemed to have picked up on the uncertainty about the scientific evidence portrayed in the media, made up their own minds, and acted accordingly. The public are more sophisticated than we give them credit for; public health messages should take this into account. If people are given absolute answers to questions for which the evidence is uncertain they seem not to believe the message.

References

i. Brown 0. Farmers fear backlash from consumers. Daily Telegraph 1996 Mar 21:l.

ii. Little K, Palmer D, Swiers D. Something to beef about? Nursing Standard 1995;9:19-21,

iii. Delasnerie-Laupretre N, Poser S, Pocchiari M, Wientjens DPWM, Will R, Creutzfeldt-Jakob disease in Europe. Lancet 1995;346:898-9.

Advisory committee's conclusion was based on "absence of any credible alternative"

ANNE WICKHAM
EDITOR - On 20 March the Spongiform Encephalopathy Advisory Committee in Britain issued a statement regarding 10 cases of Creutzfeldt-Jakob disease that showed a previously unrecognised and consistent pattern of disease.[i] The committee concluded: "in the absence of any credible alternative the most likely explanation at present is that these cases are linked to exposure to BSE (Bovine spongiform encephalopathy) before the introduction of the SBO [specified bovine offal) ban in 1989." How can a committee of scientists come to a conclusion on the basis of no credible alternative? Why exposure to bovine spongiform encephalopathy and not to microwave ovens, high voltage power lines, or organophosphorus sheep dips?

These few words have caused an epidemic of hysteria across Europe and paralysed the British beef industry at home and abroad. Pharmaceutical companies are being besieged by patients concerned about the possible risks of medicines of bovine origin. For example, diabetic patients are asking whether they should continue to take beef insulin (in the case of the pharmaceutical company to which I am a medical adviser the insulins are made from pancreases from cattle outside the British Isles).

Another concern is that the suicide rate in British farmer - which is currently among the highest by occupation in Britain - will increase and that the increase will exceed the number of deaths from Creutzfeldt-Jakob disease over the coming months. All this when, in the committee's own words, "there is no direct evidence of a link."

References

i. Brown P. Bovine spongiform encephalopathy and Creutzfeldt-Jakob disease. BMJ 1996 312,790-1 (30 March.)

Government policy has failed

MARTIN McKEE, JENNIFER A ROBERTS, TIM LANG

EDITOR - Several weeks ago two of us expressed concern about the credibility of government advice on public health.[i] The issue of bovine spongiform encephalopathy has confirmed the disbelief with which some government pronouncements on public health are regarded in Britain and worldwide. If this situation is not to be repeated lessons must be learnt from three failures of policy.

The deregulatory culture in Britain contributed to the failure to regulate recycling of sheep remains until 1989, although the Royal Commission on Environmental Pollution had expressed concern about this in 1979,[ii] Ministers have taken minimal action, which has consistently been based on the most optimistic scenarios.[iii] Deregulation is justified largely on financial grounds. Comparison of the total costs that will be incurred in Britain with those of more regulatory policies elsewhere shows that this is not tenable. Amazingly, the government confirmed its intention to relax further regulations on food hygiene immediately after a worldwide ban on the export of British beef was proposed.[iv] But food safety is not the only aspect of public health affected by deregulation: there are concerns about the effect of deregulation in, for example, the water, nuclear, and transport industries.

The second failure of policy was the way in which the Spongiform Encephalopathy Advisory Committee worked, and this was compounded by the absence from the committee, until recently, of specialist public health scientists. In the face of uncertainty, traditional methods of assessing evidence should be supplemented with techniques such as modelling of the consequences of best and worst case scenarios. Had the committee done this it might have placed less faith in the species barrier, given that many human infections originated in animals. It might also have questioned the official confidence in the implementation of precautions, given extensive evidence that they are not being taken. It also failed to appreciate how risk is perceived, which led to a patronising impression, characterised by the secretary of state's statement that "it is the public who are mad rather than the cows."

The third failure arises from the relation between the government and business in Britain. The Ministry of Agriculture, Fisheries and Food continues to resist proposals for an independent food standards agency,[v] giving the impression that commercial interests come before those of the public. A national food policy council is also needed to coordinate the many interests involved. There are many other issues, such as the presence of pesticide residues in fruit and vegetables, on which consumer opinion will demand a source of authoritative, independent advice. The public is concerned that intensive farming has cut corners in cutting costs. On grounds of public health and confidence in governance this cannot continue,

References

i. McKee M, Lane T. Secret government: the Scott report. BMJ 1996;312:455-6. (24 February)

ii. Royal Commission on Environmental Pollution. Agriculture and pollution. Seventh report: London HMSO, 1979:16. (Cmnd 7644.)

iii. Pearce F, Ministers hostile to advice on BSE New Scientist 1996 Mar 30:4-5.

iv. Shrimsley R. Ministers seek to cut red tape on food hygiene. Daily Telegraph 1996 Mar 26:4.

v. Ministry of Agriculture, Fisheries and Food. BSE: question and answer brief London: MAFF. 1996.

Risk to human populations is remote

STUART NEILSON
EDITOR - Many commentaries on bovine spongiform encephalopathy have focused concern on recent unusual cases of Creutzfeldt-Jakob disease, an apparently important increase in the incidence of the disease, and statistical accretions in particular age and occupational groups. A link between the two diseases raises the possibility (even if not the probability) of risk to large numbers of people.[i] Indeed, the standardised mortality ratios for deaths due to Creutzfeldt-Jakob disease reported to the Office of Population Censuses and Surveys during the 15 years 1919-93 show a significant excess in 1992 (chi-squared=11.67, P less than 0.01) and the interval 1987-93 (chi-squared = 4.29, P less than 0.05). The age adjusted mortality rose by 30%, from 0.6 to 0.8 deaths per million.

Deaths from Creutzfeldt-Jakob disease in the two intervals 1979-85 and 1987-93 can also, however, be viewed as two samples taken from a common distribution, with the earlier sample being less complete than the later. The difference between the two distributions of cumulative mortality was minimal (chi-squared=0.151, df=16, P greater than 0.999), and a two by two analysis of the proportion of deaths below age 45 during the two intervals (8.8% and 11%respectively) did not show a significant difference (chi-squared=0.261, df=1, P=0.61). The rise in overall mortality to date is therefore more likely to be attributable to increased awareness of Creutzfeldt-Jakob disease than to an increased risk of death.

Standard survival modelling techniques[ii] indicate that there is a small subpopulation susceptible to death due to Creutzfeldt-Jakob disease, whose relatively high mean age at death could potentially be reduced by exposure to a triggering agent derived from cattle. In particular, the mortality is well fit by a multistage (Weibull) mortality distribution[iii] in which mortality rises as the seventh power of age (for all ages) and the risk of death is restricted to about 70 per million of the general population, or about 3500 people.

Figure 1 compares the distributions of theoretical and observed mortality in 1979-85 (chi-squared =1.42, df=19, P greater than 0.999) and 1987-93 (chi-squared=0.329 df= 19, P greater than 0.999) and also shows the projected effect of a 50% increase in exposure to risk. Declining mortality after age 67 can be explained by the reduction in the number of susceptible people

The earlier age at onset noted in cases with identified polymorphisms [iv] may merely reflect the difficulties of genetic analysis and detection of familial associations in late onset cases. while bovine spongiform encephalopathy may represent a risk to these select people, there is no evidence that it has done so. STUART NEILSON

References

ii. Gore S. Bovine Creutzfeldt-Jakob disease? BMJ 1996 312,790-1 (30 March.)

ii. Neilson S, Robinson I. Reinterpreting mortality statistics: some uses of Gompertzian analysis in epidemiological research, J Clin EpidemioI 1993;41:1063-9.

iii. Doll R, The age distribution of cancer: implications for models of carcinogenesis. Journal of the Royal Statistical Society 1971; 134:133-66

iv. Brown P. Transmissible human spongiform encephalopathy (infections cerebral amyloidosis): Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome and kuru. In CaIne D B, ed, Neurodegenerative disease. Philadelphia: WB Saunders, 1994:839-76.

CJD toll among farmers `too high for mere chance'

August 15, 1997 PA News
John von Radowitz and Andrew Woodcock
Microbiologist Richard Lacey, billed in this story as the first to suggest a link between CJD and BSE seven years ago, was cited in this story as saying that the number of cattle farmers falling victim to Creutzfeld-Jakob Disease is much too high to be mere chance, adding that, "Where the CJD Surveillance Unit come unstuck is in trying to explain what happened to these six farmers. This is just too many to have occurred by chance. Unfortunately they don't want to consider the possibility that these farmers in this country and other countries were infected by cattle before BSE developed."

The story notes that professor Lacey believes sporadic CJD itself originates from a cattle infection - possibly a precursor to BSE that has not yet been detected, adding that,

"For years I have suggested that the cause is a rare disease in cattle world wide. Both BSE and the new variant CJD are a new and different disease. What has probably happened is that BSE is a variant of the old type of disease, which could have been missed because it's symptom free. It would explain why such an unusually high number of dairy farmers are being affected by CJD both here and abroad."
He also said that cases of sporadic CJD had been recorded as far back as the 1920s. Professor Lacey went on to add that he thought the new variant pattern was alarming, adding, "It's rising, and that is a concern. Unfortunately we can't predict the scale of the problem. If the disease doubled each year up to the year 2020 you'd have hundreds of thousands of cases."

Family's CJD anguish as daughter's life ebbs away

August 15, 1997 PA news Sara Naylor Marie McGivern today described, according to this story, the agony of watching her teenage daughter's life ebb away from an incurable brain disease believed to be CJD. She was cited as saying a doctor dismissed the symptoms, which began in January, as "growing pains". The family's concerns grew when the condition of their daughter, formerly a champion athlete and dancer, worsened. The story states that the day after their daughter's 15th birthday the family received news that she was probably suffering from CJD, adding, "It's terrible, we are all concerned for (her) and its just breaking all our hearts." The story adds that the daughter's mind is almost completely gone and her mother said she is like a baby.

German jailed for mad cow disease extortion bid

August 15, 1997
Reuter
KONSTANZ -- A German who tried to extort millions of marks from Swiss Nestle's Maggi unit by threatening to inject its food products with BSE was jailed for three years and two months on Friday. The sentence comes as German police investigated a new extortion attempt on Thomy, a sister company of Maggi within the multinational Nestle food group.

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