Harvard Center for Risk Analysis

Evaluation of the Potentialfor BSE in the United States

Joshua T. CohenKeith Duggar

George M. GraySilvia Kreindel

Harvard Center for Risk AnalysisHarvard School of Public Health

Hatim AbdelrahmanTsegaye HabteMariam

David OryangBerhanu Tameru

Center for Computational EpidemiologyCollege of Veterinary Medicine

Tuskegee University

Harvard Center for Risk Analysis

What USDA Asked Us to Do

• Identify and characterize possible sources for BSE (or a TSE disease with similar clinical and pathologic signs as BSE - will refer to as BSE for brevity) infectivity in U.S. cattle

• Identify and characterize pathways for cattle-derived BSE infectivity in the U.S. cattle herd or human food supply

• Evaluate implications over time of possible introduction of BSE into US system

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How We Got Involved

• HSPH/HCRA

• Group with long history in risk analysis of hazards to human health and the environment

• Expertise in methods of risk analysis

• Multidisciplinary approach

• TU/CCE

• Expertise in the integration of quantitative modeling, expert systems and operations research methods in studying the epidemiology of health systems

• Strong record of work on animal health issues

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Our Approach

• Understand the science

• Describe potential pathways of BSE infectivity to U.S. herd or food supply

• Build quantitative model

• Characterize the response of the US system BSE

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Learning from UK Experience

We assume the prevailing hypothesis of UK BSE spread is correct:

RenderingFeed BSECattle

Scrapie?Spontaneous?

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Cattle Population

Number Infected

Number Clinical 

Slaughter   

Rendering and Feed Production 

Infectivity Sources  

Human Food 

Disposal

Death and Disposal

Other Uses and Elimination from System

Other Protein Sources

Feed Administered

to Cattle

Death and Rendering

Simulation Overview

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Important Attributes of Model

• Built up from knowledge of science and agriculture system

• Probabilistic - results are distributions

• Infectivity characterized as cattle oral ID50s

• Characterize average situation across the US

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Relative Infectivity of Specific Tissues Specified From an Infected Bovine (Based on (SSC, 1999a))a

Tissue Fraction of Total Infectivity Brain No infectivity in cattle < 32 months post-inoculation (PI)

32 months PI and over: 64.1% Trigeminal Ganglia No infectivity in cattle < 32 months post-inoculation.

32 months PI and over: 2.6% Other Head (eyes, etc.) No infectivity in cattle < 32 months post-inoculation.

32 months PI and over: 0.04% Distal Ileum 6-18 months post inoculation: 100%

18-31: No Infectivity 32 months PI and over 3.3%

Spinal Cord No infectivity in cattle < 32 months post-inoculation.

32 months PI and over: 25.6% infectivity Dorsal Root Ganglia No infectivity in cattle < 32 months post-inoculation.

32 months PI and over: 3.8 % infectivity

Notes: a. The post-inoculation time values in this table reflect the assumption that the incubation period is 36

months. See text for explanation.

Key Assumptions

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Relationship between time since infection and the fraction of maximal level of ID50s

Key Assumptions

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Sick Animal Characteristics 3.1.2.1

Antemortem Inspection

3.1.2.2

Disposition of Brain

3.1.2.5

Stunning

3.1.2.3

Exsanguination

3.1.2.4

Tissues to rendering

Splitting

3.1.2.6

Postmortem Inspection

3.1.2.9

Tissues for Possible Human Consumption

5.2.10

AMR/ Spinal Cord/DRG

3.1.2.7

Processing

3.1.2.9

The Slaughter Process

Out Out Out

Out Out

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Analyses

• Base Case• Assume BSE not currently present in US• Introduce 10 BSE infected animals (also

simulated importation of 1 to 500 BSE infected cows)

• Follow for 20 years

• Example Risk Management Options• Ban on rendering cattle that die on farm• UK-style “Specified Risk Material” ban• Test with introduction of 10 infected

animals and follow for 20 years

• Others• Potential for pre ‘89 imports from

England to introduce BSE to US• Switzerland• Spontaneous• Scrapie as source

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Results: Introduction of 10 Infected Cattle

after 20 Years

• Few new cases of BSE (mean 2.9, 95th 11)• Primarily through feed ban leaks• 40% of animals predicted to die on farm

introduce 96% of infectivity to system

• BSE gone within 20 years of introduction

• Little infectivity for potential human exposure (mean 35 cattle oral ID50s , 95th 170)

• Brain 26%• Beef on bone 11%• AMR meat 56%• Spinal Cord 5%

• Conservative assumptions (e.g, no change if case detected)

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Base Case – Import 10 Infected Animals1000 Simulation Runs

Label Mean 5th 25th 50th 75th 95th

Epidemic StatisticsTotal Infected 13 10 10 10 10 21Total Infected w/o Imports 2.9 0 0 0 0 11Total Clinical 4.8 2 3 4 5 8Probability N Infected > 0 0

Mode of InfectionMaternal 0 0 0 0 0 0Spontaneous 0 0 0 0 0 0Protein 2.9 0 0 0 0 11Blood 0.003 0 0 0 0 0Exogenous 0 0 0 0 0 0

Mode of DeathSlaughter 7.4 3 4 6 7 13Die on Farm - Render 4.7 1 3 4 5 8Die on Farm - No Render 0.78 0 0 1 1 3

ID50 SourcesFrom Slaughter 1,500 260 520 830 1,300 5,800From Death on Farm 37,000 10,000 20,000 30,000 40,000 62,000

Disposition of ID50s1 To Prohibited MBM 3,600 170 1,200 2,100 3,200 12,0002 Eliminated by SRM ban 0 0 0 0 0 03 Eliminated by Rendering 35,000 10,000 20,000 30,000 39,000 60,0004 To NP MBM - Contamination 0.022 0 0 0 0 0.00335 To NP MBM - Mislabeling 190 0 0 0 7.9 1,0006 Out After Rendering 1,300 0.064 30 200 1,100 10,0007 To Prohibited Feed 2,500 33 300 1,200 2,200 11,0008 To NP Feed - Misdirected 6.2 0 0 0 0 0.49 To NP Feed - Contamination 0.031 0 0 0 0 0.002510 To NP Feed - Mislabeling 70 0 0 0 0.0066 26011 To Blood 0.38 0 0.032 0.16 0.4 1.412 Out After Feed Production 2,500 49 340 1,200 2,200 11,00013 Misfed to Cattle 17 0 0 0 0 2.614 Total to Cattle 37 0 0 0 0.075 10015 Total Potential to Humans 35 0.11 5.5 12 24 170

Potential Human ExposureBrain 9.2 0 0 0 0 0.032Spinal Cord 1.7 0 0 0 0 0Blood 0.012 0 0 0 0 0.077Distal Ileum 0.75 0 0 0 0 1.8Contaminated Organ Meat 0 0 0 0 0 0Eyes 0.00042 0 0 0 0 0Contaminated Muscle Meat 0.092 0.00072 0.0022 0.036 0.08 0.32AMR 20 0.0062 5.1 10 16 61Beef on Bone 3.8 0 0 0 3.1 23Trigeminal Ganglia 0 0 0 0 0 0

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Base Case -- Import 10 Infected AnimalNumber of Cattle Infected

Probability of Value Exceeding Zero

1.000 1.000 1.000 1.0000.972

0.661

0.293

0.121

0.062 0.050 0.034 0.022 0.012 0.008 0.004 0.004 0.004 0.003 0 0 0

prob SUM

0

0.100

0.200

0.300

0.400

0.500

0.600

0.700

0.800

0.900

1.000

Year

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Base Case -- Import 10 Infected AnimalNumber of Cattle Infected

Range of Values

Number of Cattle Infected

1

10

100

Year

0 10 20

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Base Case -- Import 10 Infected AnimalNumber of Cattle Clinical

Range of Values

Number of Cattle Clinical

0

1

2

3

4

5

6

Year

0 10 20

Base Case -- Import 10 Infected AnimalNumber of Cattle Clinical

Probability of Value Exceeding Zero

0 0

0.061

0.455

0.489

0.251

0.093

0.0460.034 0.027

0.015 0.011 0.007 0.002 0 0.001 0 0.001 0 0 0

prob SUM

00.0200.0400.0600.0800.1000.1200.1400.1600.1800.2000.2200.2400.2600.2800.3000.3200.3400.3600.3800.4000.4200.4400.4600.4800.500

Year

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

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Base Case -- Import 10 Infected AnimalID50s to Humans by Tissue

Range of Values

Number of ID50s

0.01

0.10

1.00

10.00

100.00

1000.00

10000.00

Tissue Group

All Tissues Brain Spinal Cord Blood Distal Ileum Contaminated Organ MeatEyes Contaminated MuscleAMR Beef on BoneTrigeminal Ganglia

Base Case -- Import 10 Infected AnimalID50s to Humans by Tissue

Probability that Quantity Exceeded Zero

FREQ. Prob SUM

1000 1.00

1000 0.05

1000 0.04

1000 0.12

1000 0.08

1000 0.00

1000 0.01

1000 1.00

1000 0.97

1000 0.38

1000 0.00

label

11 Trigeminal Ganglia

10 Beef on Bone

09 AMR

08 Contaminated Muscle

07 Eyes

06 Contaminated Organ Meat

05 Distal Ileum

04 Blood

03 Spinal Cord

02 Brain

01 All Tissues

Prob SUM

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

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Other Importations

0

500

1000

1500

2000

2500

0 100 200 300 400 500 600

Number of BSE-Infected Cattle Imported

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Key Uncertainties

Total Infected: MEAN

10

20

30

40

50

60

70

80

Parameter

01 AM Inspector02 Maternal Trans.03 Die on Farm Render Rate04 Misfeed Rate05 Feed Contam. Fraction06 Feed MisLabel Prob.07 Feed Contam. Prob.08 Human Food Inspection09 ID50s per Clin BSE Case10 Render Reduction Factor11 MBM Contam. Fraction12 MBM Mislabel Prob.13 MBM Contam. Prob.14 Splitter15 Stunner

16 Total to Humans: MEAN

10

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

Parameter

01 AM Inspector02 Maternal Trans.03 Die on Farm Render Rate04 Misfeed Rate05 Feed Contam. Fraction06 Feed MisLabel Prob.07 Feed Contam. Prob.08 Human Food Inspection09 ID50s per Clin BSE Case10 Render Reduction Factor11 MBM Contam. Fraction12 MBM Mislabel Prob.13 MBM Contam. Prob.14 Splitter15 Stunner

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Results: Risk Management Options

• Evaluate 2 potential risk management options - test with 10 imported BSE cows

• UK-style ban on specified risk material (brain, spinal cord, etc) in human and animal food

• Reduces BSE cases by 80%

• Reduces potential human exposure by 95%

• Ban on rendering cattle that die on the farm

• Reduces BSE cases by 77%

• Reduces potential human exposure by 20%

• Managing risk upstream makes feed ban compliance less important

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USA - SRM Ban1000 Simulation Runs

Label Mean 5th 25th 50th 75th 95th

Epidemic StatisticsTotal Infected 11 10 10 10 11 12Total Infected w/o Imports 0.51 0 0 0 1 2Total Clinical 4.5 2 3 4 6 7Probability N Infected > 0 0

Mode of InfectionMaternal 0.49 0 0 0 1 2Spontaneous 0 0 0 0 0 0Protein 0.007 0 0 0 0 0Blood 0.007 0 0 0 0 0Exogenous 0 0 0 0 0 0

Mode of DeathSlaughter 5.6 3 5 6 7 8Die on Farm - Render 0 0 0 0 0 0Die on Farm - No Render 4.9 2 4 5 6 8

ID50 SourcesFrom Slaughter 1,200 260 520 780 1,300 3,000From Death on Farm 0 0 0 0 0 0

Disposition of ID50s1 To Prohibited MBM 2.7 0.052 0.52 1.1 2.3 112 Eliminated by SRM ban 1,100 250 500 760 1,200 3,0003 Eliminated by Rendering 31 4.6 12 20 31 934 To NP MBM - Contamination 0.000043 0 0 0 0 05 To NP MBM - Mislabeling 0.12 0 0 0 0 0.456 Out After Rendering 1 0 0.00073 0.1 0.61 5.17 To Prohibited Feed 1.7 0.00049 0.11 0.61 1.3 7.88 To NP Feed - Misdirected 0.0048 0 0 0 0 5.3E-69 To NP Feed - Contamination 0.000058 0 0 0 0 010 To NP Feed - Mislabeling 0.065 0 0 0 0 0.1111 To Blood 0.3 0 0.029 0.14 0.34 0.8312 Out After Feed Production 2 0.012 0.28 0.88 1.7 8.613 Misfed to Cattle 0.039 0 0 0 0 014 Total to Cattle 0.11 0 0 0 0.011 0.3515 Total Potential to Humans 1.7 0.00076 0.0031 0.08 0.42 6.2

Potential Human ExposureBrain 0 0 0 0 0 0Spinal Cord 0 0 0 0 0 0Blood 0.01 0 0 0 0 0.046Distal Ileum 0 0 0 0 0 0Contaminated Organ Meat 0 0 0 0 0 0Eyes 0 0 0 0 0 0Contaminated Muscle Meat 0.079 0.00071 0.0021 0.018 0.079 0.23AMR 0 0 0 0 0 0Beef on Bone 1.6 0 0 0 0.096 6.1Trigeminal Ganglia 0 0 0 0 0 0

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USA - SRM BanID50s to Humans

Range of Values

ID50s to Humans

0.01

0.10

1.00

10.00

100.00

Year

0 10 20

USA - SRM BanID50s to Humans by Tissue

Probability that Quantity Exceeded Zero

FREQ. Prob SUM

1000 0.998

1000 0.000

1000 0.000

1000 0.110

1000 0.000

1000 0.000

1000 0.000

1000 0.998

1000 0.000

1000 0.328

1000 0.000

label

11 Trigeminal Ganglia

10 Beef on Bone

09 AMR

08 Contaminated Muscle

07 Eyes

06 Contaminated Organ Meat

05 Distal Ileum

04 Blood

03 Spinal Cord

02 Brain

01 All Tissues

Prob SUM

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

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USA - No Rendering of Animals that Die on Farm1000 Simulation Runs

Label Mean 5th 25th 50th 75th 95th

Epidemic StatisticsTotal Infected 11 10 10 10 11 12Total Infected w/o Imports 0.68 0 0 0 1 2Total Clinical 4.4 2 3 4 6 7Probability N Infected > 0 0

Mode of InfectionMaternal 0.5 0 0 0 1 2Spontaneous 0 0 0 0 0 0Protein 0.17 0 0 0 0 0Blood 0.007 0 0 0 0 0Exogenous 0 0 0 0 0 0

Mode of DeathSlaughter 5.9 3 5 6 7 9Die on Farm - Render 0 0 0 0 0 0Die on Farm - No Render 4.8 2 4 5 6 7

ID50 SourcesFrom Slaughter 1,200 260 530 820 1,300 3,100From Death on Farm 0 0 0 0 0 0

Disposition of ID50s1 To Prohibited MBM 110 2.5 26 48 84 3802 Eliminated by SRM ban 0 0 0 0 0 03 Eliminated by Rendering 1,100 230 480 740 1,200 2,7004 To NP MBM - Contamination 0.00033 0 0 0 0 05 To NP MBM - Mislabeling 4.3 0 0 0 0 256 Out After Rendering 37 0 0.08 3.3 26 2507 To Prohibited Feed 69 0.099 3.5 28 53 2808 To NP Feed - Misdirected 0.41 0 0 0 0 0.0000699 To NP Feed - Contamination 0.00074 0 0 0 0 010 To NP Feed - Mislabeling 2.5 0 0 0 0 811 To Blood 0.3 0 0.036 0.16 0.37 0.8112 Out After Feed Production 71 0.27 4.9 28 54 28013 Misfed to Cattle 0.8 0 0 0 0 014 Total to Cattle 1.4 0 0 0 0.031 2.515 Total Potential to Humans 28 0.15 5.5 11 24 120

Potential Human ExposureBrain 6.9 0 0 0 0 0.045Spinal Cord 1.9 0 0 0 0 0Blood 0.021 0 0 0 0 0.11Distal Ileum 0.57 0 0 0 0 0Contaminated Organ Meat 0 0 0 0 0 0Eyes 0.00046 0 0 0 0 0Contaminated Muscle Meat 0.073 0.00072 0.0022 0.016 0.079 0.19AMR 16 0.0062 5.1 10 16 51Beef on Bone 1.9 0 0 0 0.71 23Trigeminal Ganglia 0 0 0 0 0 0

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USA - No Rendering of Animals that Die on FarmID50s to Humans by Tissue

Probability that Quantity Exceeded Zero

FREQ. Prob SUM

1000 0.998

1000 0.054

1000 0.035

1000 0.124

1000 0.045

1000 0.000

1000 0.006

1000 0.998

1000 0.971

1000 0.343

1000 0.000

label

11 Trigeminal Ganglia

10 Beef on Bone

09 AMR

08 Contaminated Muscle

07 Eyes

06 Contaminated Organ Meat

05 Distal Ileum

04 Blood

03 Spinal Cord

02 Brain

01 All Tissues

Prob SUM

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

USA - No Rendering of Animals that Die on FarmID50s to Humans by Tissue

Range of Values

Number of ID50s

0.01

0.10

1.00

10.00

100.00

1000.00

10000.00

Tissue Group

All Tissues Brain Spinal Cord Blood Distal Ileum Contaminated Organ MeatEyes Contaminated MuscleAMR Beef on BoneTrigeminal Ganglia

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Imports from England before 1989

• Evaluated potential for 173 (of 334) English imports not known to have been destroyed to introduce infectivity to US cattle and implications

• Used information on birth year, export year, animal type and sex, last sighting and more to estimate likelihood and potential magnitude of introductions of BSE infectivity to US cattle feed

• Used model to look at new BSE cases if introduction of different sizes did occur

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Results: Introduction of Infectivity through

UK Imports

• 82% chance of no introduction

• Most introduction give no new cases

• Surveillance rules out big introductions

• If introduced, is on course for elimination

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Cumulative Distribution for U.S. Cattle Exposure to Cattle Oral ID50s from

Animals Imported from England during the 1980s

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Cumulative Distribution for the Number of BSE-Clinical Cattle in the Year 2000

for Different Levels of Infectivity Introduced via Import of UK Cattle

During the 1980s

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Other Results:

• Switzerland

• Test of model plausibility

• Reasonably reproduces time course and size of Swiss BSE outbreak

• Spontaneous

• If true would result in mean of 2 cases per year and <100 cattle oral ID50s to humans over 20 years

• Test in absence of feed ban casts some doubt of plausibility of this hypothesis

• Scrapie

• If transmission possible (no American scrapie can infect cattle) predict mean of 2 BSE cases/yr

• <100 cattle oral ID50s to humans over 20 years

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Summary

• We have assessed the potential for BSE/TSE infectivity to spread in the US dairy/beef cattle population and in the U.S. food supply if it were to arise here

• We have constructed a simulation model to explore the dynamics of BSE following an introduction and to quantitatively evaluate the relative risk of specific pathways

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Summary

• We find that the US is highly resistant to BSE and any plausible introduction yields few new cases of disease and dies out within 20 years. Human exposure to infectious cattle tissues is quite low

• Spread in cattle herd

• Mostly due to leaks in FDA feed ban and some maternal transmission

• Animals that die on farm with provide greatest infectivity to animal feed system

• Potential human exposure

• Handling of brain and spinal cord in processing very important

• Primary routes of exposure are cattle brain, spinal cord, beef on bone and AMR meat

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Summary

• Cattle imported from UK between 1980 and 1989 have small chance of having put BSE into US herd - would be on the way to elimination if introduced

• Our approach supported by ability to reasonably mimic Swiss BSE outbreak

• Cross-species transmission of Scrapie or Spontaneous BSE, if real would result in a couple of cases of BSE and fewer than 5 cattle oral ID50s for potential human exposure each year

• Our model is useful for evaluating potential further risk management strategies

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Thank You!