InvestigationInvestigationof vCJD in of vCJD in

LeicestershireLeicestershire

Dr Philip Monk & Dr Gerry BryantDr Philip Monk & Dr Gerry Bryant

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

Where is theLeicestershire cluster?

all 5 people with vCJD lived in the Wreake or

Soar Valley areas of Leicestershire for most or all

of their lives

4

Circles drawn at radii of 5,10 and 15km

5

How was the Leicestershirecluster 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

When was BSEfirst 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

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

What measures havebeen taken to control BSE?

• June 1988 notifiable zoonotic disease June 1988 ruminant feed ban (MBM)• August 1988 compulsory slaughter of BSE cattle

(50% compensation, 100% from Feb 1990) November 1989 specified bovine offal ban (human food)• September 1990 SBO ban extended to animal food• December 1995 prohibition of MRM from spinal column of

cattle March 1996 MBM prohibited as food supplement for

any animal & recall of feed April 1996 ban on cattle over 30 months getting into

food chain & compulsory slaughter

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What are Specified Risk

Materials?

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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

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

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

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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)05

1015202530

1995 1996 1997 1998 1999 2000

Year

Case

s of

vCJ

D co

nfirm

ed

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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

What did the initialfieldwork 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

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What did we learn aboutthe 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

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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

What were we ableto 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

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What was learned thatwas 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

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How was the meatsupply chain investigated?

• information from / interviews with – MAFF & FSA

– Information from members of the public

– Butchers

– EHOs

– Auctioneers

– Farmers

– Slaughtermen

21

What is known about themeat 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

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What do we know aboutbeef 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

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What do we knowabout 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

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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

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What do we know aboutslaughterhouses 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

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What do we know aboutpractices 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

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What do we know aboutpractices 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

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What do we know aboutlocal 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

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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

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What is the hypothesis?

vCJD

cluster

evidence evidence of early of early BSE in BSE in

areaarea

whole whole carcasses carcasses

used by local used by local butchersbutchers

Friesian Friesian cattle older cattle older

at slaughterat slaughter

potential for cross-

contaminationwith brain

bovine brains removed by butchers

fed MBM early in life

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How was thehypothesis 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

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What was the likely time of exposure?Year The BSE epidemic BSE/FSE in Leicestershire19801981198219831984 First BSE symptoms19851986 BSE recognised19871988 BSE notifiable First BSE notification19891990 First FSE notification1991199219931994199519961997199819992000

First three deathsLast date of illness onset

Two deaths

Peak of BSE epidemic

Information about cases

First date of illness onset

Duration of illness

Cases aged 0 to 17

Cases aged 2 to 19

Cases aged 5 to 23

All liv

ing

in c

lus

ter a

rea

Year Butcher a Butcher b Butcher c198019811982198319841985198619871988198919901991199219931994199519961997199819992000

Last date of illness onsetTwo deaths

Information about cases

First date of illness onset

First three deaths

Duration of illness

Cases aged 0 to 17

Cases aged 2 to 19

Cases aged 5 to 23

All liv

ing

in c

lus

ter a

rea

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Is there an association betweenpeople 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

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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

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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

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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

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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

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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

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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