1. Investigation of vCJD in Leicestershire Dr Philip Monk & Dr Gerry Bryant

2. 2 What are we going to say? information about the cluster of cases information about BSE and vCJD information about beef from farm to fork the hypothesis what we found

3. 3 Where is the Leicestershire cluster? all 5 people with vCJD lived in the Wreake or Soar Valley areas of Leicestershire for most or all of their lives

4. 4 Circles drawn at radii of 5,10 and 15km

5. 5 How was the Leicestershire cluster of cases of vCJD identified? October 1998 - local paper reported 3 deaths due to vCJD –2 out of the 3 cases had lived in Queniborough 10 November 1998 - meeting with NCJDSU –cases did not represent a cluster –NCJDSU would investigate with supplementary questionnaire 12 May 2000 - GP informed LHA of patient with probable case of vCJD 12 June 2000 - NCJDSU informed LHA of a confirmed case of vCJD 4 July 2000 - meeting at Department of Health –NCJDSU reported results of previous investigation inconclusive –agreed that this was a statistically significant cluster - chance unlikely –a local investigation should be carried out

6. 6 When was BSE first recognised? identified in November 1986 cow in Sussex ill from December 1984 concluded in December 1987 that BSE emerged as a result of ingestion of a TSE agent in ruminant derived meat & bonemeal (MBM) fed to cattle origin of BSE agent unknown but thought to be either scrapie or a previously unrecognised TSE of cattle

7. 7 When did BSE first appear? to have caused the number of BSE cases seen at the peak of the epidemic (1992-93), BSE must have been present in cattle for a number of years back-calculations suggest first cases probably occurred in the 1970s average onset in cattle at 4 - 5 years old youngest clinical case aged 20 months infectious during later stages of incubation

8. 8 What measures have been taken to control BSE? June 1988notifiable zoonotic disease  June 1988ruminant feed ban (MBM) August 1988compulsory slaughter of BSE cattle (50% compensation, 100% from Feb 1990)  November 1989specified bovine offal ban (human food) September 1990SBO ban extended to animal food December 1995prohibition of MRM from spinal column of cattle  March 1996MBM prohibited as food supplement for any animal & recall of feed  April 1996ban on cattle over 30 months getting into food chain & compulsory slaughter

9. 9 What are Specified Risk Materials?

10. 10 What is vCJD? NCJDSU established in 1990 to monitor CJD in humans in 1996 identified a new variant of CJD first person affected became ill in 1994 different presentation to sporadic CJD younger age at onset median 29 years (12 to 74) rapidly progressive with death 13 months after onset (range 6 months to over three years) distinct microscopic features

11. 11 How does vCJD present? insidious onset - early symptoms common and not specific predominant psychiatric symptoms especially depression with weight-loss, apathy, personality change, often with hallucinations and delusions - may be referred to psychiatrist sensory disturbance eg numbness, pins & needles difficulty walking leading to falls - accidents common involuntary movements signs of intellectual impairment usually leads to neurological referral and investigation progresses to immobility and mutism before death

12. 12 How is vCJD diagnosed? diagnostic criteria established other disorders excluded –typical clinical picture –particular findings in the CSF (fluid from around spinal cord) –typical MRI (brain scan) appearance –negative EEG (electrical brain activity test) –abnormal prion protein in tonsil biopsy definitive diagnosis only by characteristic microscopic brain appearance at post-mortem

13. 13 How many of cases of vCJD have there been in the UK? annual numbers have shown small steady rise figures published monthly on DH website 95 confirmed and probable cases –85 confirmed –10 probable cases (5 alive)

14. 14 What were the stages in the investigation? initial fieldwork –interviewing cases –exploring all possible exposures to BSE investigating the meat supply chain in the area –cattle farming –slaughtering –butchering practices developing a theory that could explain the cluster of cases testing the theory

15. 15 What did the initial fieldwork involve? face to face interviews with at least one parent of the people with vCJD GP records examined information held by NCJDSU obtained with the consent of the relatives and reviewed questionnaire survey of parents of children at Queniborough Primary School questionnaire survey of Queniborough residents

16. 16 What did we learn about the cases? 5 people with vCJD 3 male and 2 female median age at onset 22 years (range 17 to 34) median duration of illness 14 months (range 10 to 26) onset of illness from summer 1996 to winter 1999 dates of death from summer 1998 to autumn 2000

17. 17 What period of time was investigated? to investigate these cases to find a common link, there had to be a period of time when a common exposure could have occurred because all of the people in this cluster had lived in the Wreake and Soar valley area of North Leicestershire from 1980 to 1991 this was the period we investigated

18. 18 What were we able to exclude at this stage? surgery and blood transfusions dental surgery immunisations occupational exposure injections, body piercing, cuts and animal bites baby foods, school meals & drinking water manganese

19. 19 What was learned that was important ? all cases ate beef & beef products investigation narrowed to meat supply no single supplier links all of the cases all had eaten beef from local retail butchers in the area questionnaire surveys of Queniborough people suggested that most families usually shopped at supermarkets

20. 20 How was the meat supply chain investigated? information from / interviews with –MAFF & FSA –Information from members of the public –Butchers –EHOs –Auctioneers –Farmers –Slaughtermen

21. 21 What is known about the meat industry in the 1980s? meat industry historically bears no resemblance to that which exists today –different breeds of beef cattle now –fewer cattle markets now –fewer slaughterhouses now –fewer ‘local’ (high street) butchers now –more meat now purchased from supermarkets

22. 22 What do we know about beef farming in the area during the 1980s? beef industry largely a by-product of the dairy industry in the cluster area cattle mostly Friesian or Friesian/Hereford cross-breeds calves raised from dairy herds fed meat and bone meal from 6 days of age rather than 6 months for suckler herds so earlier and longer exposure the BSE agent in MBM Friesian cattle excellent for milk-production, slower to fatten for beef slaughtered at close to three years

23. 23 What do we know about BSE in the area during the 1980s? early BSE –Leicestershire area had a moderately high incidence of BSE –first cases in cluster area notified in 1988

24. 24 We therefore conclude that a small number of cattle in this area could have been incubating BSE at time of slaughter during the early 1980s

25. 25 What do we know about slaughterhouses in the area during the 1980s? most cattle slaughtered in large abattoirs few small abattoirs with low throughput few butchers who slaughtered differences in slaughtering practices

26. 26 What do we know about practices in large slaughterhouses? high throughput - 60 cattle an hour captive bolt stunning pithing rods were not used carcasses hosed down at end of slaughter process to remove debris skulls sent to specialist head boning plant or to renderers after removal of head meat skulls were not split

27. 27 What do we know about practices in small slaughterhouses and slaughtering butchers? low throughput - one cattle an hour captive bolt stunning pithing rods were used carcasses wiped down at end of slaughter process to remove debris whole carcass including the head usually passed on to butcher for processing

28. 28 What do we know about local retail butchers used by the cases during the early 1980s? used small slaughterhouse or slaughtered on premises used and processed whole carcass including head split cattle heads and removed brain –had a market for whole brain splitting skulls is difficult and messy if the membrane covering brain is broken, brain which is gelatinous, has a tendency to stick to things

29. 29 The hypothesis the people who developed vCJD were exposed to the BSE agent by consumption of beef carcass meat purchased from butchers where there was a risk of cross-contamination with bovine brain during the boning, jointing and cutting process where butchers split the heads of beasts to remove the brain

30. 30 What is the hypothesis? vCJD cluster evidence of early BSE in area whole carcasses used by local butchers Friesian cattle older at slaughter potential for cross- contamination with brain bovine brains removed by butchers fed MBM early in life

31. 31 How was the hypothesis tested? formal matched case-control study –face to face recorded interviews with a relative of each case and a relative of each of thirty controls (six for each case) –drawn from same local population with possibility of similar exposures as cases –representative of the local population explored usual beef consumption and purchasing habits during 1980-85 and 1986-90 –shopping habits –usual menus investigation of butchering practices of the meat suppliers

32. 32 What was the likely time of exposure ?

33. 33 Is there an association between people who developed vCJD and the consumption of beef between 1980 and 1985 from a butcher where there was a potential risk of contamination of meat with brain tissue? risk unknown for 1 case and 1 control –used most conservative estimate where data not known extremely strong association between those with the disease and this type of exposure before 1985 statistically significant very unlikely to be a chance finding no association found after 1985

34. 34 What does this mean? this association may explain four out of the five cases in this cluster this suggests that the incubation period for these people may have been from 10 to 16 years suggests a low infectious dose

35. 35 What are the limitations of these findings? case control study driven by findings from fieldwork which may have pointed us in the wrong direction but we have demonstrated an extremely strong association the theory is biologically plausible

36. 36 What are the key elements?  the beasts used were locally reared predominantly Friesian cattle fed MBM from day 6 onwards giving them a greater lifetime exposure to feedstuff that was potentially contaminated with the BSE agent  slaughtered at close to three years in small abattoirs which employed pithing and without the washing down of the carcass  when heads were split to remove the brain, if the membrane covering the brain was broken, brain material was likely to stick to meat and surfaces because it is of a gelatinous consistency  carcasses were wiped with cloths increasing the risk of cross-contamination

37. 37 How unusual was this practice? we identified 4 out of 22 butchers who practised this way legitimate practice traditional butchering craft only became illegal to use brains after the SBO ban of 1989

38. 38 What do we recommend? Locally –continued surveillance Nationally –this hypothesis needs to be tested for other cases of vCJD –consideration of these findings by those responsible for reviewing the measures taken to continue to protect the public from BSE

39. 39 Acknowledgements relatives of cases and controls residents of cluster area all who have given us information University of Leicester Local Authorities Communicable Disease Surveillance Centre National CJD Surveillance Unit London School of Hygiene & Tropical Medicine Department of Health Ministry of Agriculture Fisheries & Food Food Standards Agency