Update on Bovine Spongiform Encephalopathy

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Update onBovine Spongiform Encephalopathy

• FDA TSE Advisory Committee Meeting
• Holiday Inn
• Gaithersburg MD
• 20 February 2003
• David M. Asher, MD
• ltasher_at_cber.fda.govgt
• Laboratory of Bacterial, Parasitic
  Unconventional Agents
• Division of Emerging Transfusion-Transmitted
  Diseases
• Office of Blood Research Review
• Center for Biologics Evaluation Research

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BSE Update

• Variant CJD cases, trends, implications
• BSE
• World distribution
• New countries
• Risk assessments (USDA, EC GBR)
• WHO warning
• Control measures
• Additional measures to protect human food
• EC and national actions on animal TSEs
• EC legislation
• National actions (example)
• Compliance?

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141 Cases of Probable or Confirmed Variant CJD
(vCJD) in Six Countriesthrough Jan 2003

• UK - 131 (total definiteprobable 119 dead)
• France - 6
• Ireland 1
• Italy - 1
• US 1
• Canada 1
• Spain 1 possible, under investigation
• ---------------------------------
• Long-time UK residents

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Age Distribution of CJD in UKCJD and vCJD
1994-2001(Taffs R al. FDA Science Forum 2002)
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130 vCJD Cases in UK (Will R et al, CJD
Surveillance Unit, Edinburgh, unpublished)
Mean age at death 29 yr (range
14-74) Median age at death 28
yr Mean age at onset 27 yr
(range 12-74) Median age at onset
26 yr Median duration of illness 14 months
(range 6-39) 72 males 58 females 111 UK cases
tested were MM at codon 129 of the PrP-encoding
(PRNP) gene. Of 139 worldwide cases, 121 tested
were MM at codon129 of the PRNP gene.
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22 Countries with BSE in Native Cattleyr first
reported approx. total cases reported to OIE
thro Jan 2003

• UK 1986 (gt182 581) 1443 in 2000 1202 in 01
  755 in 02
• Ireland 1989 (1150)
• Switzerland 1990 (420)
• France 1991 (692)
• Portugal 1994 (699)
• Belgium 1997 (98)
• Netherlands 1997 (52)
• Luxembourg 1997 (2)
• Liechtenstein 1998 (2)
• Denmark 2000 (10)
• Germany 2000 (235)

• Spain 2000 (210)
• Italy 2000 (56)
• Greece 2001 (1)
• Czech Repub 2001 (2)
• Slovakia 2001 (10)
• Japan 2001 (7 or ?8)
• Slovenia 2001 (2)
• Finland 2001 (1)
• Austria 2001 (1)
• Poland 2002 (4)
• Israel 2002 (1)

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BSE Incidence per 106 Cows gt 24 mo old
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Opinion of the Scientific Steering Committee of
the EC Directorate General SANCO on
theGeographical Risk of Bovine Spongiform
Encephalopathy (GBR)adopted 11 January 2002
(modified from Final Opinion of July 2000)

• Qualitative method to assess BSE risk in regions
  or countries
• Not intended to assess human exposure risk
• Voluntary submission of dossiers by countries
• Systematic evaluation of risk factors by expert
  committees
• Dynamic risk changes as situations change

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EC Geographical Risk of Bovine Spongiform
Encephalopathy (GBR)Eight Risk Factors to
Consider

• Cattle population and dynamics
• Trade in animals
• Animal feed controls
• Prohibition of meat-and-bone meal
• Specified risk materials controlled
• Surveillance
• Controls on rendering and feed preparation
• Culling of sick and at-risk animals

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EC Geographical Risk of Bovine Spongiform
Encephalopathy (GBR)Two Main Composite Factors
to Consider

• External challenge (probability that BSE agent
  entered a country)
• Live cattle imports
• Meat-and-bone meal imports
• Internal Stability (probability that BSE agent
  would amplify and spread in a country)
• Feeding practices MBM ban in place
• Rendering practices
• SRM removal
• Surveillance of BSE
• Cross-contamination controls

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EC GBR Assumptions

• BSE is restricted to bovines among food animals
• Theoretical risk of infection of sheep and goats
  acknowledged but ignored
• Only sources of BSE agent are imports of infected
  cattle or bovine-derived materials
• Theoretical risk of spontaneous generation of
  infectivity ignored
• Transmission vector is contaminated feed
• Theoretical risks of maternal, contact, field
  contamination ignored
• Surveillance systems have intrinsic limitations
• Risk assessment cannot rely on confirmed cases

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Definition of the Geographical BSE Risk its
levelsUpdate of the Opinion of the Scientific
Steering Committee of the EC Directorate General
SANCO on the Geographical Risk of Bovine
Spongiform Encephalopathy (GBR) adopted 11
January 2002 (modified from original Final
Opinion of July 2000)
GBR level Presence of one or more cattle clinically or pre-clinically infected with the BSE agent in a geographical region/country
I Highly unlikely
II Unlikely but not excluded
III Likely but not confirmed or confirmed at a lower level
IV Confirmed at a higher level
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Two EC GBR IV Countries

• United Kingdom
• Portugal (mainland)

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31 Countries in EC GBR III

• Albania
• Austria
• Belgium
• Bulgaria
• Croatia
• Cyprus
• Czech Republic
• Denmark
• Finland
• France
• Germany
• Greece
• Hungary
• Ireland (Republic)
• Israel

• Italy
• Japan
• Latvia
• Lithuania
• Luxembourg
• Malta
• Netherlands
• Poland
• Romania
• San Marino
• Slovak Republic
• Slovenia
• Spain
• Switzerland
• Turkey

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Nine Countries in EC GBR II

• Canada
• Colombia
• India
• Kenya
• Mauritius

• Nigeria
• Pakistan
• Sweden
• USA

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17 Countries in EC GBR I

• Argentina
• Australia
• Botswana
• Brazil
• Chile
• Costa Rica
• El Salvador
• Namibia
• New Zealand

• Nicaragua
• Norway
• Panama
• Paraguay
• Singapore
• Swaziland
• Uruguay
• Vanuatu

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Predictive Record of EC GBR

• Correctly predicted case of BSE in native cattle
  (GBR III)
• Germany
• Italy
• Spain
• Czech Republic
• Slovak Republic
• Denmark
• Greece
• Japan (would have)
• Israel (would have)

• Did not correctly predict BSE in native cattle
  (originally assigned GBR II)
• Austria
• Finland
• Slovenia

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Measures to protect humans from food-borne
exposures to BSE agent(FDA TSEAC Jan 2002)

• Effective control of BSE in cattle and small
  ruminants (sheep and goats)
• OIE-compliant national surveillance programs
  (Active surveillance testing of brain tissues
  from animals at increased risk of BSE)
• Prohibitions on feeding most mammalian proteins
  to ruminants (feed bans) and steps to prevent
  accidental feeding of prohibited proteins
• Prompt condemnation and destruction of animals
  with signs of BSE
• Preventive culling of animals at increased risk
• Adequate compensation to owners (encourages
  compliance)

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Measures to protect humans from food-borne
exposures to BSE agent(TSEAC Jan 2002 continued)

•  Age-based slaughter schemes
• Intended to reduce risk by prohibiting
  consumption of meat products from ruminants
  slaughtered after an age when substantial amounts
  of BSE agent are likely to be present in tissues,
  generally taken to be no later than 24 to 30
  months for cattle
• Example UK Over-Thirty-Month Rule

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Measures to protect humans from food-borne
exposures to BSE agent(TSEAC Jan 2002 continued)

• Separation of high-risk materials from edible
  meat products
• Prohibition of slaughter methods that may
  embolize brain tissue, possibly contaminating
  meat, e.g. intracranial air injection and
  pithing
• Removal of specified risk materials (SRMCNS,
  lymphoid, intestinal tissues) from ruminant
  carcasses at the time of slaughter and effective
  segregation of SRM from edible materials
• Prohibition of advanced or mechanical meat
  recovery systems (may contaminate meat with
  ganglia, spinal cord, possibly brain)

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Measures to protect humans from food-borne
exposures to BSE agent(TSEAC Jan 2002 continued)

• Application of same measures to protect the human
  food chain to imported food and domestically
  produced food
• Effective compliance with all above to be
  verified by
• Inspections
• Audits

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WHO Suggests Eight Questions from Consumers for
National Authorities(Understanding the BSE
Threat WHO 2002)

1. What are cattle fed?
2. Is there active surveillance for BSE?
3. Are cases of BSE imported or born in the
   countrys own herd?
4. Does meat come from young cattle?
5. Are high-risk tissues removed and destroyed?
6. Are procedures in place to prevent
   cross-contamination?
7. Are there any other meat products that could
   contain BSE agent?
8. Are safe practices stringently controlled?

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Regulation (EC) No 999/2001 of the European
Parliament and of the Council of 22 May
2001laying down rules for the prevention,
control and eradication of certain transmissible
spongiform encephalopathies

• Applies to production and marketing of live
  animals and animal-derived products.
• Applies to products intended for food, feed,
  fertilizer.
• Does not apply to cosmetics, medicinal products
  or medical devices (other rules apply).
• Rules apply to all EC Member States

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Regulation (EC) No 999/2001

• Member States should
• Monitor BSE and scrapie in annual active programs
  to include rapid PrPTSE tests.
• Designate, remove and safely dispose of SRMs.
• Prohibit feeding of certain proteins to certain
  animals.
• Notify authorities of suspect TSE animals and
  quarantine carcasses until diagnosis.
• Destroy TSE carcasses and identify other animals
  at risk, restrict their movements and compensate
  owners.

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Regulation (EC) No 999/2001 (continued)

• Member States should also
• Prohibit marketing of certain products from
  bovines in high-risk regions but allow certain
  products produced under controlled conditions
  from animals demonstrated not posing high risk.
• Establish Reference Laboratories for TSE tests
  including rapid PrPTSE tests.
• Carry out inspections and audits of EC Member
  States and third countries.
• Reassess BSE status when OIE develops suitable
  procedures (proposes 5 categories instead of GBR
  I-IV).

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Regulation (EC) No 999/2001 (Annex)

• Five EC Proposed BSE categories
• BSE-free No BSE, no risk, all requirements met
  ?7 yr, no MBM in feed ? 8 yr.
• Provisionally BSE-free No indigenous BSE but
  history of risk and compliant as for 1).
• Similar to 2) but with a few indigenous cases of
  BSE ?7 yr ago and compliant but not for ?7 yr
  c
• Low BSE incidence ?1/106 but ?100/106 animals
  ?24 mo old.
• High BSE incidence ?100/106 animals ?24 mo old.

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Example of National ActionAgence Française de
Sécurité Sanitaire des Aliments (AFSSA) Recent
Opinions on Animal TSEshttp//www.afssa.fr/avis/i
ndex.asp?id

• 2001 (33 opinions)
• 2002 (26 opinions very loosely translated)
• 3 Jan BSE control
• 16 Jan Animal feeds
• 10 Feb TSEs of small ruminants
• 6 Mar Beef labels
• 12 Mar Farmed game meat
• 25 Mar Traceability of sheep and goats
• 28 Mar Slaughter houses
• 28 Mar Modified TSE orders
• 16 Apr Swiss cattle

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Agence Française de Sécurité Sanitaire des
Aliments (AFSSA) Recent Opinions on Animal TSEs
(continued)

• 2002
• 25 Apr Fertilizers
• 7 May Transport of animal products
• 16 May Transport of food
• 31 May Comment on Bosque al (TSE infectivity
  in rodent muscle)
• 31 May Screening tests for small ruminants
• 13 June Survey SRM retrieval in slaughterhouses
• 18 June Mechanical meat recovery
• 27 June Spinal cord removal from small ruminants
• 24 July Animal feeds

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Agence Française de Sécurité Sanitaire des
Aliments (AFSSA) Recent Opinions on Animal TSEs
(continued)

• 2002
• 27 Aug Sanitary meat production, mkting (mod.)
• 5 Sept Do and slaughterhouse inspections
• 19 Sept Risk assessment for beef
• 9 Oct Proposed modification of BSE controls
• 15 Oct Proposed modification of UK imports
• 4 Nov Scrapie control measures
• 14 Nov Marketing of scrapie contact sheep/goats
• 20 Dec Proposed rule change regarding direct
  sale of sheep and goat carcasses containing
  spinal cord

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Useful web addresses for BSE information (partial
listing)

• European Commission http//europa.eu.int/comm/food
  /fs/bse/index_en.html
• France http//www.afssa.fr/avis/index.asp?id
• Switzerland http//www.bvet.admin.ch/index_bse.htm
  l
• UK Food Standards Agency http//www.foodstandards.
  gov.uk/bse/facts
• WHO http//www.who.int/emc/diseases/bse/index.html